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  • 301.
    Aquilonius, S-M
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Some patophysiological aspects on motor fluctuations in Parkinson's disease in Treatment of Parkinson's Disease and Parkinsonism1996Chapter in book (Other scientific)
  • 302.
    Aquilonius, S-M
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Fagius, Jan
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Den neurologiska undersökningen2000In: Neurologi, Liber AB , 2000, p. 58-Chapter in book (Other scientific)
  • 303.
    Aquilonius, S-M
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Naver, Hans
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Injektioner av botulinumtoxin kan ersätta nervavskärning1998In: Läkartidningen, Vol. 35, p. 3658-Article in journal (Other scientific)
  • 304.
    Aquilonius, Sten-Magnus
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. neurologi.
    Amyotrofisk lateralscleros2007In: Hjärnan, Karolinska Institutet University Press, Stockhoolm , 2007Chapter in book (Other scientific)
  • 305.
    Aquilonius, Sten-Magnus
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Neurologi.
    Neurologi i utveckling2004In: Incitament, p. 5-Article, review/survey (Other (popular scientific, debate etc.))
  • 306.
    Aquilonius, Sten-Magnus
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. neurologi.
    Ny utgåva av neuroanatomisk klassiker: Per Brodal: The central nervous system2005In: Läkartidningen, p. 505-Article, book review (Other (popular scientific, debate etc.))
  • 307.
    Aquilonius, Sten-Magnus
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. neurologi.
    Om att breda sin smörgås2006In: Läkartidningen, Vol. 103, no 11, p. 830-Article in journal (Other (popular scientific, debate etc.))
  • 308.
    Aquilonius, Sten-Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Parkinson's disease: Swedish pioneering research on pathophysiology and treatment2012In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 19, no S1, p. 841-841Article in journal (Other academic)
  • 309.
    Aquilonius, Sten-Magnus
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. neurologi.
    Rörelsestörningar2006In: Neurologi, Liber AB Stockholm , 2006, p. 568-Chapter in book (Other scientific)
  • 310.
    Aquilonius, Sten-Magnus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry.
    Dahllöf, Tell Åke
    Droger och desperation i skilda världar: missbruk av katinon och metkatinon hotar hälsa och social utveckling.2009In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 106, no 20, p. 1358-1361Article, review/survey (Other academic)
    Abstract [sv]

    De betydande sociala och medicinska riskerna vid missbruk av katinon (tuggning av kat) och metkatinon (intravenös injektion av illegala synteser) har i stort sett inte uppmärksammats i svensk narkotikadebatt.

    Tullens beslag av kat visar hur det traditionella bruket importeras med immigration från framför allt Östafrika.

    Syntesrecept på metkatinon, som kan hämtas från Internet, ger produkter som orsakat manganförgiftning med svåra, irreversibla motoriska handikapp hos hundratals unga framför allt i Baltikum, Ryssland, Ukraina och Georgien. Denna »epidemi« fortgår.

    Kunskap om förekomst, kliniska symtom och spridningsrisker vid dessa missbruksformer är angelägen såväl ur ett nationellt som ett internationellt biståndsperspektiv.

  • 311.
    Aquilonius, Sten-Magnus
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. neurologi.
    Boman, Gunnar
    Department of Medical Sciences.
    Nyholm, Dag
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. neurologi.
    Från Alzheimer till övervikt2007Book (Other (popular scientific, debate etc.))
  • 312.
    Aquilonius, Sten-Magnus
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. neurologi.
    Fagius, Jan
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. neurologi.
    Den neurologiska undersökningen2006In: Neurologi, Liber AB Stockholm , 2006, p. 568-Chapter in book (Other scientific)
  • 313.
    Aquilonius, Sten-Magnus
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. neurologi.
    Fuxe, Kjell
    Striatal plasticity in health and disease: SWEMODIS symposium, Nobel Forum2004Conference proceedings (editor) (Refereed)
  • 314.
    Aquilonius, Sten-Magnus
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. neurologi.
    Lees, Andrew
    Managing advanced Parkinson's disease: the role of continuous dopaminergic stimulation2007Book (Other scientific)
  • 315.
    Aquilonius, Sten-Magnus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Development of new levodopa treatment strategies in Parkinson’s disease – from bedside to bench to bedside2017In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 122, no 2, p. 71-77Article, review/survey (Refereed)
    Abstract [en]

    This review will illustrate the process of moving from an idea through preclinical research and Galenic developments into clinical investigations and finally to approval by regulatory agencies within the European Union. The two new treatment strategies described, levodopa/carbidopa intestinal gel and levodopa/carbidopa microtablets, for advanced Parkinson's disease, have been developed in collaborative research within departments at Uppsala University. With this historical approach, reference priority is given to reports considered to be of special importance for this more than two decades long process from bedside to bench to bedside'.

  • 316.
    Aquilonius, Sten-Magnus
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Neurologi.
    Widner, Håkan
    Utveckling inom motorikområdet2004In: Incitament, p. 7-9Article, review/survey (Other (popular scientific, debate etc.))
  • 317. Arakelian, Erebouni
    et al.
    Färdig, Martin
    Nyholm, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Nurses anaesthetists' versus patients' assessment of anxieties in an ambulatory surgery setting.2019In: Journal of perioperative practice, ISSN 2515-7949, article id 1750458919838198Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Failure to assess patients' anxiety perioperatively by means of a validated instrument makes the assessment arbitrary. Studies are lacking about how well nurse anaesthetists estimate patients' preoperative worries.

    PURPOSE: To compare the nurse anaesthetists' estimations of patients' preoperative anxieties with the patients' own assessment of their anxieties.

    DESIGN: Quantitative prospective design.

    METHODS: Eighty-five pairs of patients and nurse anaesthetists in two ambulatory surgery units in a university hospital in Sweden were included. Patients' perioperative anxieties were graded using the Numeric Visual Analogue Anxiety Scale.

    RESULTS: The nurse anaesthetist overestimated the patients' level of preoperative anxiety in 53% of patients and underestimated patients' anxieties in 31% of the patients. Consensus was seen in 16% of the pairs. In fifty-six pairs (65%), the difference between the estimation of level of patients' anxiety according to Numeric Visual Analogue Anxiety Scale was between -3 (overestimation) and +3 levels (underestimation). Median levels of anxiety were estimated as 3 within the patient group and 4 among the nurse anaesthetists.

    CONCLUSIONS: Systematic assessment of patients' level of anxiety could lead to identifying patients with severe anxiety levels and to offer more individualised treatment. The patients' own estimation must form the basis for the discussion and treatment.

  • 318.
    Arakelian, Erebouni
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Laurssen, Emma
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Öster, Caisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Older Patients' Worries in Connection With General Anesthesia and Surgery - A Qualitative Study2018In: Journal of Perianesthesia Nursing, ISSN 1089-9472, E-ISSN 1532-8473, Vol. 33, no 6, p. 822-833Article in journal (Refereed)
    Abstract [en]

    Purpose: To examine anxiety and what older patients worry about related to anesthesia and colorectal surgery, and their perceptions regarding nurses' ability to ease preoperative worry.

    Design: Qualitative individual face-to-face interviews.

    Methods: The study included 18 patients aged between 62 and 91 years with lower abdominal tumors. The study was conducted in two day-surgery wards in Sweden. Interview data were analyzed with Malterud's systematic text condensation.

    Findings: Four themes were identified: (1) losing control of one's body, leaving one's life in someone else's hands, and the feeling that there is no going back, (2) claustrophobia and anticipated pain in an unknown environment, (3) unknown and frightening vocabulary concerning the surgery, and (4) what can happen if something goes wrong.

    Conclusions: Patients worry about a number of things. If preoperative worry could be identified, actions taken to reduce worry could be personalized and patients' own strategies to reduce worries may be helpful for them.

  • 319.
    Arakelian, Erebouni
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Nyholm, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Öster, Caisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ekselius: Psychiatry.
    How Anesthesiologists and Nurse Anesthetists Assess and Handle Patients' Perioperative Worries Without a Validated Instrument2019In: Journal of Perianesthesia Nursing, ISSN 1089-9472, E-ISSN 1532-8473, Vol. 34, no 4, p. 810-819Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To study how nurse anesthetists and anesthesiologists assess and handle patients' perioperative anxiety without using a validated instrument.

    DESIGN: Qualitative study.

    METHODS: Individual in-depth face-to-face interviews were conducted with nurse anesthetists (n = 9) and anesthesiologists (n = 5) from a university hospital in Sweden. Data were analyzed with thematic analysis according to Braun and Clark.

    FINDINGS: Two themes were identified: (1) I ask about anxiety, look for visual signs, and observe communication and (2) I handle patients' anxieties individually. In addition to subthemes describing assessment and handling of adults, it appeared that parents played an important role in children's perioperative anxiety.

    CONCLUSIONS: When not using a validated instrument, assessing perioperative anxiety is commonly based on the anesthesiologist's and nurse anesthetist's experience, knowledge, views, and attitudes. The evaluator's capability of using different strategies in the assessment and handling of perioperative anxiety is important.

  • 320. Araç, Demet
    et al.
    Aust, Gabriela
    Calebiro, Davide
    Engel, Felix B
    Formstone, Caroline
    Goffinet, André
    Hamann, Jörg
    Kittel, Robert J
    Liebscher, Ines
    Lin, Hsi-Hsien
    Monk, Kelly R
    Petrenko, Alexander
    Piao, Xianhua
    Prömel, Simone
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Schwartz, Thue W
    Stacey, Martin
    Ushkaryov, Yuri A
    Wobus, Manja
    Wolfrum, Uwe
    Xu, Lei
    Langenhan, Tobias
    Dissecting signaling and functions of adhesion G protein-coupled receptors2012In: Annals of the New York Academy of Sciences, ISSN 0077-8923, E-ISSN 1749-6632, Vol. 1276, no 1, p. 1-25Article in journal (Refereed)
    Abstract [en]

    G protein-coupled receptors (GPCRs) comprise an expanded superfamily of receptors in the human genome. Adhesion class G protein-coupled receptors (adhesion-GPCRs) form the second largest class of GPCRs. Despite the abundance, size, molecular structure, and functions in facilitating cell and matrix contacts in a variety of organ systems, adhesion-GPCRs are by far the most poorly understood GPCR class. Adhesion-GPCRs possess a unique molecular structure, with extended N-termini containing various adhesion domains. In addition, many adhesion-GPCRs are autoproteolytically cleaved into an N-terminal fragment (NTF, NT, α-subunit) and C-terminal fragment (CTF, CT, β-subunit) at a conserved GPCR autoproteolysis-inducing (GAIN) domain that contains a GPCR proteolysis site (GPS). These two features distinguish adhesion-GPCRs from other GPCR classes. Though active research on adhesion-GPCRs in diverse areas, such as immunity, neuroscience, and development and tumor biology has been intensified in the recent years, the general biological and pharmacological properties of adhesion-GPCRs are not well known, and they have not yet been used for biomedical purposes. The "6th International Adhesion-GPCR Workshop," held at the Institute of Physiology of the University of Würzburg on September 6-8, 2012, assembled a majority of the investigators currently actively pursuing research on adhesion-GPCRs, including scientists from laboratories in Europe, the United States, and Asia. The meeting featured the nascent mechanistic understanding of the molecular events driving the signal transduction of adhesion-GPCRs, novel models to evaluate their functions, and evidence for their involvement in human disease.

  • 321. Archer, T
    et al.
    Bassen, M
    Peters, D
    Luthman, J
    Fredriksson, A
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Dopaminergic-glutamatergic balance in the forebrain: functional studies of movement disorders in rats and mice. In: Palomo T, Archer T, Beninger RJ, editors. Dopamine disease states.1996Chapter in book (Other scientific)
  • 322. Archer, T
    et al.
    Fredriksson, A
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    An antihypokinesic action of alpha2-adrenoceptors upon MPTP-induced behaviour deficits in mice2003In: J Neural Trasm, Vol. 110(2), p. 183-Article in journal (Refereed)
  • 323. Archer, T
    et al.
    Fredriksson, A
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Effect of clonidine and alpha-adrenoceptor antagonists on motor activity in DSP4-treated mice I: dose-, time- and parameter-dependency.2000In: Neurotoxicity Res, Vol. 1, p. 235-Article in journal (Refereed)
  • 324. Archer, T
    et al.
    Fredriksson, A
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Effects of acute/chronic, subthreshold/threshold doses of L-Dopa in MPTP-treated mice: In:T. Palomo, R.J.Beninger & T. Archer (eds) Interactive monoaminergic Basis of Brain Disorders.1998Chapter in book (Other scientific)
  • 325. Archer, T
    et al.
    Fredriksson, A
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Restoration and putative protectionof MPTP-induced functional deficits. In: Palomo T, Beninger RJ, Archer T (eds). Neurodegerative Brain Disorders2000Chapter in book (Other scientific)
  • 326. Archer, T
    et al.
    Fredriksson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Functional consequences of iron overload in catecholaminergic interactions: the Youdim factor2007In: Neurochemical Research, ISSN 0364-3190 (Print) 1573-6903 (Online), Vol. 32, no 10, p. 1625-1639Article, review/survey (Refereed)
    Abstract [en]

    The influence of postnatal iron overload upon implications of the functional and interactive role of dopaminergic and noradrenergic pathways that contribute to the expressions of movement disorder and psychotic behaviours in mice was studied in a series of experiments. (1) Postnatal iron overload at doses of 7.5 mg/kg (administered on Days 10–12 post partum) and above, invariably induced a behavioural syndrome consisting of an initial (1st 20–40 min of a 60-min test session) hypoactivity followed by a later (final 20 min of a 60-min test session) hyperactivity, when the mice were tested at adult ages (age 60 days or more). (2) Following postnatal iron overload, subchronic treatment with the neuroleptic compounds, clozapine and haloperidol, dose-dependently reversed the initial hypoactivity and later hyperactivity induced by the metal. Furthermore, DA D2 receptor supersensitivity (as assessed using the apomorphine-induced behaviour test) was directly and positively correlated with iron concentrations in the basal ganglia. (3) Brain noradrenaline (NA) denervation, using the selective NA neurotoxin, DSP4, prior to administration of the selective DA neurotoxin, MPTP, exacerbated both the functional (hypokinesia) and neurochemical (DA depletion) effects of the latter neurotoxin. Treatment with L-Dopa restored motor activity only in the animals that had not undergone NA denervation. These findings suggest an essential neonatal iron overload, termed “the Youdim factor”, directing a DA–NA interactive component in co-morbid disorders of nigrostriatal-limbic brain regions.

  • 327. Archer, T.
    et al.
    Fredriksson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, Ulleråker, University Hospital.
    Johansson, B.
    Exercise alleviates Parkinsonism: clinical and laboratory evidence2011In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 123, no 2, p. 73-84Article, review/survey (Refereed)
    Abstract [en]

    The present review examines the putative benefits for individuals afflicted with Parkinsonism, whether in the clinical setting or in the animal laboratory, accruing from different exercise regimes. The tendency for patients with Parkinson's disease (PD) to express either normal or reduced exercise capacity appears regulated by factors such as fatigue, quality-of-life and disorder severity. The associations between physical exercise and risk for PD, the effects of exercise on idiopathic Parkinsonism and quality-of-life, the effects of exercise on animal laboratory models of Parkinsonism and dopamine (DA) loss following neurotoxic insults, and the effects of exercise on the DA precursor, L-Dopa, efficacy are examined. It would appear to be case that in view of the particular responsiveness of the dopaminergic neurons to exercise, the principle of 'use it or lose' may be of special applicability among PD patients.

  • 328. Archer, T
    et al.
    Palomo, T
    Fredriksson, A
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Functional expressions of noradrenergic receptor changes following denervation with DSP4: interactive and parametric effects of clondine. In: Palomo T, Beninger RJ, Archer T (eds) Neurodegerative Brain Disorders2000Chapter in book (Other scientific)
  • 329. Archer, T
    et al.
    Palomo, T
    Fredriksson, A
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Neonatal 6-Hydroxydopamine-induced Hypo/hyperactivity: Blockade by Dopamine Reuptake Inhibitors and Effect of A D-amphetamine2002In: Neurotoxicity Res, Vol. 4, p. 247-Article in journal (Refereed)
  • 330. Archer, T
    et al.
    Palomo, T
    McArthur, R
    Fredriksson, A
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Effects of acute administration of DA agonists on locomotor activity: MPTP versus neonatal intracerebroventricular 6-OHDA treatment.2003In: Neurotox Res, Vol. 5(1-2), p. 95-Article in journal (Refereed)
  • 331. Archer, T
    et al.
    Schroder, N
    Fredriksson, A
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Neurobehavioural deficits following postnatal iron overload: II Instrumental learning performance2003In: Neurotox Res, Vol. 5, p. 77-Article in journal (Refereed)
  • 332. Archer, Trevor
    et al.
    Fredriksson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Behavioural supersensitivity following neonatal 6-hydroxydopamine: Attenuation by MK-8012007In: Neurotoxicity research, ISSN 1029-8428, E-ISSN 1476-3524, Vol. 12, no 2, p. 113-124Article in journal (Refereed)
    Abstract [en]

    Male rat pups were administered 6-hydroxydopamine (6-OHDA, 75 μg, intracisternally, 30 min after desipramine, 25 mg/kg, s.c.) on Days 1 or 2 after birth, or were sham-operated (receiving vehicle). In four experiments, the acute effects of apomorphine, with or without pretreatment with MK-801 (0.03 mg/kg), upon motor activity in test chambers was measured. Acute treatment with apomorphine (0.1 mg/kg) increased locomotor, rearing and total activity markedly compared to both the acute saline administered 6-OHDA rats and the sham-operated rats administered saline. Acute MK-801 (0.03 mg/kg) co-administered shortly before (5 min) apomorphine (0.3 or 1.0 mg/kg) reduced markedly locomotion and total activity in 6-OHDA-treated and sham-operated rats. Rearing behaviour was increased in both the 6-OHDA groups of rats. Acute MK-801 increased activity in the 6-OHDA-treated rats, which was not observed in sham-operated rats. At the 0.3 and 1.0 mg/kg doses of apomorphine, neonatal 6-OHDA treament increased all three parameters of motor activity. Acute treatment with apomorphine (0.1 mg/kg) induced different effects on the motor activity of 6-OHDA-treated and sham-operated mice. In sham-operated rats apomorphine reduced motor activity during the 1st 30-min period but increased locomotion and total activity, but not rearing, during the 2nd and 3rd periods, whereas in 6-OHDA-treated rats, apomorphine increased locomotor, rearing and total activity markedly. Dopamine loss and serotonin elevation in the striatum and olfactory tubercle were confirmed. The present findings confirm the influence of non-competitive glutamate antagonists in attenuating the behavioural supersensitivity to dopamine antagonists.

  • 333. Archer, Trevor
    et al.
    Fredriksson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Delayed Exercise-Induced Functional and Neurochemical Partial Restoration Following MPTP2012In: Neurotoxicity research, ISSN 1029-8428, E-ISSN 1476-3524, Vol. 21, no 2, p. 210-221Article in journal (Refereed)
    Abstract [en]

    In two experiments, MPTP was administered to C57/BL6 mice according to a single-dose weekly regime (MPTP: 1 x 30 mg/kg on the fifth day of the week, Friday, over 4 weeks) with vehicle group (Vehicle: 1 x 5 ml/kg) treated concurrently. Exercise schedules (delayed) were introduced either at the beginning of the week after the second MPTP injection (MPTP + Exercise(2) group), or at the beginning of the week after the fourth MPTP injection (MPTP + Exercise(4) group). Wheel-running was provided on the first 4 days of each week (Monday-Thursday) more than 30-min periods. In Experiment I, wheel-running exercise was introduced either after 2 or 4 weeks after MPTP/Vehicle. MPTP and Vehicle groups not provided access to the running wheels were placed in single cages within the wheel-running room over 30-min concomitantly with the wheel-running groups. In Experiment II, wheel-running exercise was introduced 2 weeks after MPTP/Vehicle but a no-exercise control group with non-revolving wheel included (MPTP-Wheel). In both experiments, spontaneous motor activity tests during 60-min intervals were performed at the end (Fridays) of weeks 1, 2, 3, 4, 6, 8, and 10, where the week on which the first injection of MPTP was the first week; in the case of weeks 1-4, this was immediately before MPTP/Vehicle injections. It was observed that the introduction of the exercise schedule after the second MPTP injection, but not after the fourth injection, restored motor activity that had been markedly elevated by the end of the tenth week. Subthreshold administration of l-dopa tests was performed after the spontaneous motor activity tests 6, 8 and 10; these indicated significant effects of exercise, MPTP + Exercise(2) group, on Tests 6 and 8, but not Test 10. The physical exercise schedule in that group also showed markedly attenuated loss of dopamine (DA). Restoration of MPTP-induced motor activity deficits and DA loss was a function of the point at which exercise was introduced, in the present case after two administrations of the neurotoxin. In Experiment II, physical exercise markedly attenuated the hypokinesic effect of MPTP in the exercise condition, MPTP-exercise, but not in the non-exercise conditions, MPTP-Cage and MPTP-Wheel, for both spontaneous motor activity and l-dopa-induced activity. MPTP-induced loss of DA was also attenuated by exercise.

  • 334. Archer, Trevor
    et al.
    Fredriksson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, Ulleråker, University Hospital.
    Influence of noradrenaline denervation on MPTP-induced deficits in mice2006In: Journal of neural transmission, ISSN 0300-9564, E-ISSN 1435-1463, Vol. 113, no 9, p. 1119-1129Article in journal (Refereed)
    Abstract [en]

    C57/BL6 mice were administered either DSP4 (50 mg/kg, s.c., 30 min after injection of zimeldine, 20 Cemg/kg, s.c.) or vehicle (saline) at 63 days of age. Three weeks later, one group (n = 10) of DSP4-treated and one group of vehicle-treated mice were administered MPTP (2 x 40 mg/kg, s.c., 24 hours between injections; the High dose groups), one group (n = 10) of DSP4-treated and one group of vehicle-treated mice were administered MPTP (2 x 20 mg/kg, s.c., 24 hours between injections; the Low dose groups), and one group (n = 10) of DSP4-treated and one group of vehicle-treated mice were administered vehicle. Three weeks later, all six groups were tested in motor activity test chambers, followed by injections of L-Dopa (20 mg/kg, s.c.), and then tested over a further 360 min in the activity test chambers. It was found that pretreatment with the selective NA neurotoxin, DSP4, deteriorated markedly the dose-dependent motor activity deficits observed in the vehicle pretreated MPTP treated mice. These 'ultra-deficits' in the spontaneous motor behaviour of MPTP-treated mice were observed over all three parameters: locomotion, rearing and total activity, and were restricted to the 1(st) and 2(nd) 20-min periods. Administration of L-Dopa (20 mg/kg) following the 60-min testing of spontaneous behaviour restored the motor activity of Vehicle + MPTP treated mice (neither the Vehicle + MPTP-Low nor the Vehicle + MPTP-High groups differed from the Vehicle-Vehicle group, here) but failed to do so in the DSP4 pretreated mice. Here, a dose-dependent deficit of L-Dopa-induced motor activity (over all three parameters) was obtained thereby offering further evidence of an 'ultra-deficit' of function due to previous denervation of the NA terminals. The present findings support the notion that severe damage to the locus coeruleus noradrenergic system, through systemic DSP4, disrupts the facilitatory influence on the nigrostriatal DA system, and interferes with the ability of the nigrostriatal pathway to compensate for or recover from marked injury, MPTP treatment.

  • 335.
    Archer, Trevor
    et al.
    Department of Psychology, University of Gothenburg.
    Fredriksson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, Ulleråker, University Hospital. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Physical Exercise Attenuates MPTP-Induced Deficits in Mice2010In: Neurotoxicity research, ISSN 1029-8428, E-ISSN 1476-3524, Vol. 18, no 3-4, p. 313-327Article in journal (Refereed)
    Abstract [en]

    Two experiments were performed to investigate the effects of physical exercise upon the hypokinesia induced by two different types of MPTP administration to C57/BL6 mice. In the first, mice were administered either the standard MPTP dose (2 x 20 or 2 x 40 mg/kg, 24-h interval) or vehicle (saline, 5 ml/kg); and over the following 3 weeks were given daily 30-min period of wheel running exercise over five consecutive days/week or placed in a cage in close proximity to the running wheels. Spontaneous motor activity testing in motor activity test chambers indicated that exercise attenuated the hypokinesic effects of both doses of MPTP upon spontaneous activity or subthreshold l-Dopa-induced activity. In the second experiment, mice were either given wheel running activity on four consecutive days (30-min period) or placed in a cage nearby and on the fifth day, following motor activity testing over 60 min, injected with either MPTP (1 x 40 mg/kg) or vehicle. An identical procedure was maintained over the following 4 weeks with the exception that neither MPTP nor vehicle was injected after the fifth week. The animals were left alone (without either exercise or MPTP) and tested after 2- and 4-week intervals. Weekly exercise blocked, almost completely, the progressive development of severe hypokinesia in the MPTP mice and partially restored normal levels of activity after administration of subthreshold l-Dopa, despite the total absence of exercise following the fifth week. In both experiments, MPTP-induced loss of dopamine was attenuated by the respective regime of physical exercise with dopamine integrity more effectively preserved in the first experiment. The present findings are discussed in the context of physical exercise influences upon general plasticity and neuroreparative propensities as well as those specific for the nigrostriatal pathway.

  • 336. Archer, Trevor
    et al.
    Fredriksson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    The Yeast Product Milmed Enhances the Effect of Physical Exercise on Motor Performance and Dopamine Neurochemistry Recovery in MPTP-Lesioned Mice2013In: Neurotoxicity research, ISSN 1029-8428, E-ISSN 1476-3524, Vol. 24, no 3, p. 393-406Article in journal (Refereed)
    Abstract [en]

    Both clinical and laboratory studies have demonstrated that different types of physical exercise may alleviate Parkinsonism yet evidence for complete restoration of motor function and biomarker integrity are difficult to identify. MPTP (1 x 30 mg/kg, s.c., 4 groups) or saline (vehicle 1 x 5 ml/kg, s.c., 1 group) were administered in a single dose regime over three consecutive weeks on Fridays. Three MPTP groups were given four 30-min periods/week (Mondays to Thursdays), of these two groups, MPTP + Exer + M(i) and MPTP + Exer + M(ii); the former were introduced to exercise and Milmed (oral injection) on the week following the 1st MPTP injection and the latter on the Monday prior to the 1st injection of MPTP onwards. One MPTP group, MPTP + Exer, was given access to exercise (running wheels) from the week following the 1st MPTP injection onwards. The fourth MPTP group, MPTP-NoEx, and the Vehicle group were only given access to exercise on a single day each week (Wednesdays, exercise test) from the week following the 1st MPTP injection onwards. The exercise/exercise + Milmed regime was maintained for a further 9 weeks. It was observed that exercise by itself ameliorated MPTP-induced deficits regarding motor function and dopamine loss only partially whereas in the groups combining exercise with twice weekly dosages of Milmed the MPTP-induced deficits were abolished by the 10th week of the intervention. The three main conclusions that were drawn from correlational analyses of individual mice were: (i) that DA integrity was observed to be a direct function of ability to express running exercise in a treadmill wheel-running arrangement, and (ii) that DA integrity was observed to be a direct function of the capacity for motor performance as measured by spontaneous motor activity and subthreshold l-Dopa (5 mg/kg) induced activity in the motor activity test chambers, and (iii) that the extent to which running exercise in a running wheel was predictive of later motor performance in the activity test chambers was highly convincing.

  • 337. Archer, Trevor
    et al.
    Fredriksson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, Ulleråker, University Hospital.
    Schütz, Erica
    Kostrzewa, Richard M.
    Influence of Physical Exercise on Neuroimmunological Functioning and Health: Aging and Stress2011In: Neurotoxicity research, ISSN 1029-8428, E-ISSN 1476-3524, Vol. 20, no 1, p. 69-83Article in journal (Refereed)
    Abstract [en]

    Chronic and acute stress, with associated pathophysiology, are implicated in a variety of disease states, with neuroimmunological dysregulation and inflammation as major hazards to health and functional sufficiency. Psychosocial stress and negative affect are linked to elevations in several inflammatory biomarkers. Immunosenescence, the deterioration of immune competence observed in the aged aspect of the life span, linked to a dramatic rise in morbidity and susceptibility to diseases with fatal outcomes, alters neuroimmunological function and is particularly marked in the neurodegenerative disorders, e.g., Parkinson's disease and diabetes. Physical exercise diminishes inflammation and elevates agents and factors involved in immunomodulatory function. Both the alleviatory effects of life-long physical activity upon multiple cancer forms and the palliative effects of physical activity for individuals afflicted by cancer offer advantages in health intervention. Chronic conditions of stress and affective dysregulation are associated with neuroimmunological insufficiency and inflammation, contributing to health risk and mortality. Physical exercise regimes have induced manifest anti-inflammatory benefits, mediated possibly by brain-derived neurotrophic factor. The epidemic proportions of metabolic disorders, obesity, and diabetes demand attention; several variants of exercise regimes have been found repeatedly to induce both prevention and improvement under both laboratory and clinical conditions. Physical exercise offers a unique non-pharmacologic intervention incorporating multiple activity regimes, e.g., endurance versus resistance exercise that may be adapted to conform to the particular demands of diagnosis, intervention and prognosis inherent to the staging of autoimmune disorders and related conditions.

  • 338. Archer, Trevor
    et al.
    Garcia, Danilo
    Fredriksson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Restoration of MPTP-induced deficits by exercise and Milmed (R) co-treatment2014In: PeerJ, ISSN 2167-8359, E-ISSN 2167-8359, Vol. 2, p. e531-Article in journal (Refereed)
    Abstract [en]

    1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces permanent neurochemical and functional deficits. Following the administration of either two or four injections of the dopamine neurotoxin, MPTP, at a dose of 40 mg/kg, C57/BL6 mice were given access to running-wheels (30-min sessions, four times/week, Monday-Thursday) and treatment with the treated yeast, Milmed (R) (four times/week, Monday-Thursday), or simply running-wheel exercise by itself, over ten weeks. It was observed that the combination of physical exercise and Milmed (R) treatment, the MPTP + Exercise + Yeast (MC) group [MPTP + Exercise + Milmed (R) (MC)], restored spontaneous motor activity markedly by test day 10, restored completely subthreshold L-Dopa-induced activity, and dopamine concentration to 76% of control values, in the condition wherein two administrations of MPTP (2 x 40 mg/kg) were given prior to initiation of exercise and/or Milmed (R) treatment. Physical exercise by itself, MPTP + Exercise (MC) group, attenuated these deficits only partially. Administration of MPTP four times (i.e., 40 mg/kg, s.c., once weekly over four weeks for a total of 160 mg/kg, MPTP + Exercise + Yeast (MC) group [MPTP + Exercise + Milmed (R) (SC)] and MPTP + Exercise (SC), induced a lesioning effect that was far too severe for either exercise alone or the exercise + Milmed (R) combination to ameliorate. Nevertheless, these findings indicate a powerful effect of physical exercise reinforced by Milmed (R) treatment in restoring MPTP-induced deficits of motor function and dopamine neurochemistry in mice.

  • 339.
    Aresh, Bejan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Genetics.
    Functional Aspects of Peripheral and Spinal Cord Neurons Involved in Itch and Pain2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    We have investigated the role of the metabotropic glutamate receptor 7 (mGluR7) and the gastrin releasing peptide receptor (Grpr) population that are involved at different levels of itch transmission. We found that mGuR7 deficient mice displayed an anaphylaxis-like behavior when provoked with histamine. Analysis of blood revealed elevated plasma levels of histamine and mouse mast cell protease-1 (mMCP1), two indicators of anaphylaxis, in mGluR7 deficient mice compared with control mice. Inhibition of the neurokinin 1 receptor, by preventing binding of the corresponding ligand substance P (SP), prior to provocation with histamine prevented the development of anaphylaxis in mGluR7 deficient animals. However, blocking GRPR (gastrin releasing peptide receptor) only resulted in decreased itch levels in mGluR7 deficient mice but did not prevent the systemic anaphylaxis-like behavior. Our findings indicate that mGluR7 normally functions as a brake on histaminergic itch that is mediated through GRPR as well as anaphylaxis through Substance P.

    Grpr has previously been shown to mediate both histaminergic and non-histaminergic itch but little is known about the GRPR neuronal population. We used a BAC cloning strategy to construct a Grpr-Cre line, which we crossed with the reporter lines tdTomato and Viaat-egfp as well as with Vglut2-lox. We could conclude that Grpr-Cre neurons are mainly excitatory interneurons located in lamina II-IV, that convey itch using VGLUT2-mediated glutamatergic transmission to the next, currently unknown, step in the labeled line of chemical itch.

    To eventually deduce the function of the endogenous opioids dynorphin and enkephalin, which are hypothesized to be involved in gating pain and itch in the spinal cord, we constructed two Cre lines using BAC cloning that targeted the precursor proteins preprodynorphin and preproenkephalin, respectively. Preprodynorphin-Cre neurons were mainly located in lamina II-IV and overlapped to 47% with Vglut2 mRNA, while the co-expression with the inhibitory markers Viaat-egfp and PAX2 was 13% and 28% respectively in the spinal cord. Preproenkephalin neurons were more localized to lamina III in the dorsal horn, furthermore single cell analysis showed that they overlapped to 94% with Vglut2 mRNA while 7% and 13% expressed Viaat-egfp and PAX2 respectively.

    List of papers
    1. Identification of a Neuronal Receptor Controlling Anaphylaxis
    Open this publication in new window or tab >>Identification of a Neuronal Receptor Controlling Anaphylaxis
    Show others...
    2016 (English)In: Cell reports, ISSN 2211-1247, E-ISSN 2211-1247, Vol. 14, no 2, p. 370-379Article in journal (Refereed) Published
    Abstract [en]

    Allergic reactions can in severe cases induce a state of circulatory shock referred to as anaphylaxis. Histamine, the primary mediator of this condition, is released from immune cells, and, therefore, anaphylaxis has so far been considered an immune system disorder. However, we here show that the glutamatergic receptor mGluR7, expressed on a subpopulation of both peripheral and spinal cord neurons, controls histamine-induced communication through calcium-dependent autoinhibition with implications for anaphylaxis. Genetic ablation of mGluR7, and thus altered regulation of histamine-sensing neurons, caused an anaphylaxis-like state in mGluR7(-/-) mice, which could be reversed by antagonizing signaling between neurons and mast cells but not by antagonizing a central itch pathway. Our findings demonstrate the vital role of nervous system control by mGluR7 in anaphylaxis and open up possibilities for preventive strategies for this life-threatening condition.

    National Category
    Neurosciences
    Identifiers
    urn:nbn:se:uu:diva-272637 (URN)10.1016/j.celrep.2015.12.033 (DOI)000368101600019 ()26748715 (PubMedID)
    Funder
    Swedish Research CouncilRagnar Söderbergs stiftelseKnut and Alice Wallenberg FoundationÅke Wiberg FoundationMagnus Bergvall FoundationThe Royal Swedish Academy of Sciences
    Available from: 2016-01-15 Created: 2016-01-15 Last updated: 2018-01-10Bibliographically approved
    2. Spinal Cord Interneurons Expressing the Gastrin-Releasing Peptide Receptor Convey Itch Through VGLUT2-Mediated Signaling
    Open this publication in new window or tab >>Spinal Cord Interneurons Expressing the Gastrin-Releasing Peptide Receptor Convey Itch Through VGLUT2-Mediated Signaling
    Show others...
    2017 (English)In: Pain, ISSN 0304-3959, E-ISSN 1872-6623, Vol. 158, no 5, p. 945-961Article in journal (Refereed) Published
    Abstract [en]

    Itch is a sensation that promotes the desire to scratch, which can be evoked by mechanical and chemical stimuli. In the spinal cord, neurons expressing the gastrin-releasing peptide receptor (GRPR) have been identified as specific mediators of itch. However, our understanding of the GRPR population in the spinal cord, and thus how these neurons exercise their functions, is limited. For this purpose, we constructed a Cre line designed to target the GRPR population of neurons (Grpr-Cre). Our analysis revealed that Grpr-Cre cells in the spinal cord are predominantly excitatory interneurons that are found in the dorsal lamina, especially in laminae II-IV. Application of the specific agonist gastrin-releasing peptide induced spike responses in 43.3% of the patched Grpr-Cre neurons, where the majority of the cells displayed a tonic firing property. Additionally, our analysis showed that the Grpr-Cre population expresses Vglut2 mRNA, and mice ablated of Vglut2 in Grpr-Cre cells (Vglut2-lox; Grpr-Cre mice) displayed less spontaneous itch and attenuated responses to both histaminergic and nonhistaminergic agents. We could also show that application of the itch-inducing peptide, natriuretic polypeptide B, induces calcium influx in a subpopulation of Grpr-Cre neurons. To summarize, our data indicate that the Grpr-Cre spinal cord neural population is composed of interneurons that use VGLUT2-mediated signaling for transmitting chemical and spontaneous itch stimuli to the next, currently unknown, neurons in the labeled line of itch.

    Keywords
    Itch, Gastrin-releasing peptide receptor population, Natriuretic polypeptide B, Spinal cord, Vesicular glutamate transporter 2, Neuronal networks, Labeled line of itch, Electrophysiology, Conditional knockout analysis, Tracing, Calcium imaging, Grpr, VGLUT2
    National Category
    Medical and Health Sciences
    Research subject
    Medical Science
    Identifiers
    urn:nbn:se:uu:diva-284058 (URN)10.1097/j.pain.0000000000000861 (DOI)000402430600021 ()28157737 (PubMedID)
    Funder
    Swedish Research CouncilThe Swedish Brain FoundationThe Royal Swedish Academy of SciencesRagnar Söderbergs stiftelseMagnus Bergvall FoundationGunvor och Josef Anérs stiftelse
    Note

    Title in thesis list of papers: Spinal Cord Interneurons Expressing the Gastrin Releasing Peptide Receptor Convey Itch through VGLUT2-mediated Signaling

    Available from: 2016-04-14 Created: 2016-04-14 Last updated: 2017-07-10Bibliographically approved
    3. Characterization of preprodynorphin-expressing cells in the mouse nervous system
    Open this publication in new window or tab >>Characterization of preprodynorphin-expressing cells in the mouse nervous system
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Dynorphin is an endogenous opioid that has been implicated in maintaining chronic pain and gating of both itch and acute mechanical pain through acting on both opioid and non-opioid receptors. To improve our understanding of the complex and multifunctional population that expresses dynorphin, we have constructed a preprodynorphin Cre line (Pdyn-Cre) using BAC cloning. Single cell analysis of tdTomato;Pdyn-Cre cells revealed that 43% of the population expressed Pdyn mRNA, and no analyzed tdTomato;Pdyn-Cre negative cell expressed Pdyn mRNA, thus confirming that Cre had been inserted under the control of the Pdyn promoter. The Pdyn-Cre expressing population was found in the dorsal spinal cord, mainly in lamina II-IV and overlapped to 47% with Vglut2 mRNA, while co-expression with the inhibitory markers Viaat-egfp and Pax2 was 13% and 28%, respectively. The expression of Pdyn-Cre in the brain was extensive, marking virtually all cortical structures, including somatosensory and motor cortex. Furthermore, Pdyn-Cre was densely expressed in the striatum, amygdala and parts of the hippocampus, and expression was also observed in several pain and itch processing areas, including amygdala, lateral parabrachial nucleus, claustrum, insular cortex and raphe magnus nucleus. Our analysis indicates that the transgenic Pdyn-Cre line includes PDYN cells in the nervous system and will thus be useful as a transgenic tool for studies of the role and connectivity of the PDYN population.

    Keywords
    Preprodynorphin, characterization
    National Category
    Medical and Health Sciences
    Research subject
    Medical Science
    Identifiers
    urn:nbn:se:uu:diva-284066 (URN)
    Available from: 2016-04-14 Created: 2016-04-14 Last updated: 2016-06-01Bibliographically approved
    4. Characterization of preproenkephalin expressing neurons in the nervous system using a transgenic line
    Open this publication in new window or tab >>Characterization of preproenkephalin expressing neurons in the nervous system using a transgenic line
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Here we have constructed a Cre line to target preproenkephalin expressing cells (Penk-Cre) using a BAC cloning strategy. By crossing our Penk-Cre line with the tdTomato reporter, tdTomato;Penk-Cre expressing cells could be visualized. Penk-Cre was expressed throughout the dorsal spinal cord, where approximately 50% of the neurons were residing within lamina III. Furthermore, single-cell analysis of spinal Penk-Cre expressing cells showed that 41% was positive for Penk mRNA and that a majority (94%) of the population expressed Vglut2 mRNA. Immunohistochemical analysis showed that only 7% and 13% expressed the inhibitory markers Viaat-egfp and Pax2, respectively, hence identifying spinal Penk-Cre expressing neurons as mainly excitatory. The expression of Penk-Cre in the brain was extensive, including dense expression in the striatum, nucleus accumbens and several amygdaloid nuclei. Furthermore, Penk-Cre expression was also shown in insular cortex, cingulated cortex, primary and secondary somatosensory cortices and the trigeminal nuclei. The Penk-Cre line represents a useful genetic tool for future analysis of PENK expressing neurons in the nervous system.

     

    Keywords
    characterization, Cre, preproenkephalin, Penk
    National Category
    Medical and Health Sciences
    Research subject
    Medical Science
    Identifiers
    urn:nbn:se:uu:diva-284068 (URN)
    Available from: 2016-04-14 Created: 2016-04-14 Last updated: 2016-06-01Bibliographically approved
  • 340.
    Aresh, Bejan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Genetics.
    Freitag, Fabio B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Genetics.
    Perry, Sharn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Genetics.
    Blümel, Edda
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Genetics.
    Lau, Joey
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Franck, Marina C.M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Genetics.
    Lagerström, Malin C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Genetics.
    Spinal Cord Interneurons Expressing the Gastrin-Releasing Peptide Receptor Convey Itch Through VGLUT2-Mediated Signaling2017In: Pain, ISSN 0304-3959, E-ISSN 1872-6623, Vol. 158, no 5, p. 945-961Article in journal (Refereed)
    Abstract [en]

    Itch is a sensation that promotes the desire to scratch, which can be evoked by mechanical and chemical stimuli. In the spinal cord, neurons expressing the gastrin-releasing peptide receptor (GRPR) have been identified as specific mediators of itch. However, our understanding of the GRPR population in the spinal cord, and thus how these neurons exercise their functions, is limited. For this purpose, we constructed a Cre line designed to target the GRPR population of neurons (Grpr-Cre). Our analysis revealed that Grpr-Cre cells in the spinal cord are predominantly excitatory interneurons that are found in the dorsal lamina, especially in laminae II-IV. Application of the specific agonist gastrin-releasing peptide induced spike responses in 43.3% of the patched Grpr-Cre neurons, where the majority of the cells displayed a tonic firing property. Additionally, our analysis showed that the Grpr-Cre population expresses Vglut2 mRNA, and mice ablated of Vglut2 in Grpr-Cre cells (Vglut2-lox; Grpr-Cre mice) displayed less spontaneous itch and attenuated responses to both histaminergic and nonhistaminergic agents. We could also show that application of the itch-inducing peptide, natriuretic polypeptide B, induces calcium influx in a subpopulation of Grpr-Cre neurons. To summarize, our data indicate that the Grpr-Cre spinal cord neural population is composed of interneurons that use VGLUT2-mediated signaling for transmitting chemical and spontaneous itch stimuli to the next, currently unknown, neurons in the labeled line of itch.

  • 341.
    Aresh, Bejan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Genetics.
    Moelijker, Nynke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Genetics.
    Blümel, Edda
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Genetics.
    Lagerström, Malin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Genetics.
    Characterization of preproenkephalin expressing neurons in the nervous system using a transgenic lineManuscript (preprint) (Other academic)
    Abstract [en]

    Here we have constructed a Cre line to target preproenkephalin expressing cells (Penk-Cre) using a BAC cloning strategy. By crossing our Penk-Cre line with the tdTomato reporter, tdTomato;Penk-Cre expressing cells could be visualized. Penk-Cre was expressed throughout the dorsal spinal cord, where approximately 50% of the neurons were residing within lamina III. Furthermore, single-cell analysis of spinal Penk-Cre expressing cells showed that 41% was positive for Penk mRNA and that a majority (94%) of the population expressed Vglut2 mRNA. Immunohistochemical analysis showed that only 7% and 13% expressed the inhibitory markers Viaat-egfp and Pax2, respectively, hence identifying spinal Penk-Cre expressing neurons as mainly excitatory. The expression of Penk-Cre in the brain was extensive, including dense expression in the striatum, nucleus accumbens and several amygdaloid nuclei. Furthermore, Penk-Cre expression was also shown in insular cortex, cingulated cortex, primary and secondary somatosensory cortices and the trigeminal nuclei. The Penk-Cre line represents a useful genetic tool for future analysis of PENK expressing neurons in the nervous system.

     

  • 342.
    Aresh, Bejan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Genetics.
    Peuckert, Christiane
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology.
    Dissection and Culture of Mouse Embryonic Kidney2017In: Journal of Visualized Experiments, ISSN 1940-087X, E-ISSN 1940-087X, no 123, article id e55715Article in journal (Refereed)
    Abstract [en]

    The goal of this protocol is to describe a method for the dissection, isolation, and culture of mouse metanephric rudiments. During mammalian kidney development, the two progenitor tissues, the ureteric bud and the metanephric mesenchyme, communicate and reciprocally induce cellular mechanisms to eventually form the collecting system and the nephrons of the kidney. As mammalian embryos grow intrauterine and therefore are inaccessible to the observer, an organ culture has been developed. With this method, it is possible to study epithelial-mesenchymal interactions and cellular behavior during kidney organogenesis. Furthermore, the origin of congenital kidney and urogenital tract malformations can be investigated. After careful dissection, the metanephric rudiments are transferred onto a filter that floats on culture medium and can be kept in a cell culture incubator for several days. However, one must be aware that the conditions are artificial and could influence the metabolism in the tissue. Also, the penetration of test substances could be limited due to the extracellular matrix and basal membrane present in the explant. One main advantage of organ culture is that the experimenter can gain direct access to the organ. This technology is cheap, simple, and allows a large number of modifications, such as the addition of biologically active substances, the study of genetic variants, and the application of advanced imaging techniques.

  • 343.
    Aresh, Bejan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Genetics.
    Stjärne, Ludvig
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Genetics.
    Blümel, Edda
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Genetics.
    Maturi, Naga Prathyusha
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Genetics.
    Lagerström, Malin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Genetics.
    Characterization of preprodynorphin-expressing cells in the mouse nervous systemManuscript (preprint) (Other academic)
    Abstract [en]

    Dynorphin is an endogenous opioid that has been implicated in maintaining chronic pain and gating of both itch and acute mechanical pain through acting on both opioid and non-opioid receptors. To improve our understanding of the complex and multifunctional population that expresses dynorphin, we have constructed a preprodynorphin Cre line (Pdyn-Cre) using BAC cloning. Single cell analysis of tdTomato;Pdyn-Cre cells revealed that 43% of the population expressed Pdyn mRNA, and no analyzed tdTomato;Pdyn-Cre negative cell expressed Pdyn mRNA, thus confirming that Cre had been inserted under the control of the Pdyn promoter. The Pdyn-Cre expressing population was found in the dorsal spinal cord, mainly in lamina II-IV and overlapped to 47% with Vglut2 mRNA, while co-expression with the inhibitory markers Viaat-egfp and Pax2 was 13% and 28%, respectively. The expression of Pdyn-Cre in the brain was extensive, marking virtually all cortical structures, including somatosensory and motor cortex. Furthermore, Pdyn-Cre was densely expressed in the striatum, amygdala and parts of the hippocampus, and expression was also observed in several pain and itch processing areas, including amygdala, lateral parabrachial nucleus, claustrum, insular cortex and raphe magnus nucleus. Our analysis indicates that the transgenic Pdyn-Cre line includes PDYN cells in the nervous system and will thus be useful as a transgenic tool for studies of the role and connectivity of the PDYN population.

  • 344. Argiolas, A
    et al.
    Melis, MR
    Murgia, S
    Schioth, HB
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    ACTH- and alpha-MSH-induced grooming, stretching, yawning and penile erection in malerats: Site of action in the brain and role of melanocortin receptors2000In: Brain Res Bull, Vol. 51, p. 425-Article in journal (Refereed)
  • 345. Arimura, K
    et al.
    Arimura, Y
    Ng, A
    Uehara, A
    Nakae, M
    Osame, M
    Stålberg, Erik
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. neurofysiologi.
    The origin of spontaneous discharges in acquired neuromyotonia. A macro EMG study.2005In: Clin Neurophysiol, Vol. 116, p. 1835-1839Article in journal (Refereed)
  • 346.
    Arimura, K
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Arimura, Y
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Takenaga, S
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Suwazono, S
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Stalberg, E
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Pattern of stimulus-dependent jitter abnormalities in neuromuscular disorders.1996In: In:Recent advances in clinical neurophysiology. Eds: Kimura,J & Shibasaki,H, Elservier Science B.V Amsterdam , 1996, p. 276-Chapter in book (Other scientific)
  • 347. Arimura, K
    et al.
    Arimura, Y
    Takenaga, S
    Suwazono, S
    Stalberg, E
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Stimulus frequency-dependent jitter in ALS by stimulation SFEMG1995In: Electroenceph Clin Neurophysiol, Vol. 97, p. 170-Article, book review (Other scientific)
  • 348.
    Arimura, K
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Takenaga, S
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Nakagawa, M
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Osame, M
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Stalberg, E
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Stimulation single fibre EMG study in a patient with Schwartz-Jampel syndrome.1996In: J Neurol Neurosurg Psychiat, Vol. 61, p. 425-Article in journal (Refereed)
  • 349.
    Arkkukangas, Marina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Sundler, Annelie J
    Söderlund, Anne
    Eriksson, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiotherapy.
    Johansson, Ann-Christin
    Older persons' experiences of a home-based exercise program with behavioral change support2017In: Physiotherapy Theory and Practice, ISSN 0959-3985, E-ISSN 1532-5040, Vol. 33, no 12, p. 905-913Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: It is a challenge to promote exercise among older persons. Knowledge is needed regarding the maintenance of exercise aiming at preventing falls and promoting health and well-being in older persons.

    PURPOSE: This descriptive study used a qualitative inductive approach to describe older persons' experiences of a fall-preventive, home-based exercise program with support for behavioral change.

    METHODS: Semi-structured interviews were conducted with 12 elderly persons aged 75 years or older, and a qualitative content analysis was performed.

    RESULTS: Four categories emerged: facilitators of performing exercise in everyday life, the importance of support, perceived gains from exercise, and the existential aspects of exercise.

    CONCLUSION: With support from physiotherapists (PTs), home-based exercise can be adapted to individual circumstances in a meaningful way. Including exercises in everyday life and daily routines could support the experience of being stronger, result in better physical functioning, and give hope for an extended active life in old age.

  • 350. Arkkukangas, Marina
    et al.
    Söderlund, Anne
    Eriksson, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiotherapy.
    Johansson, Ann-Christin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Fall Preventive Exercise With or Without Behavior Change Support for Community-Dwelling Older Adults: A Randomized Controlled Trial With Short-Term Follow-up2019In: Journal of Geriatric Physical Therapy, ISSN 1539-8412, E-ISSN 2152-0895, Vol. 42, no 1, p. 9-17Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: In Western countries, falls and fall-related injuries are a well-known threat to health in the aging population. Studies indicate that regular exercise improves strength and balance and can therefore decrease the incidence of falls and fall-related injuries. The challenge, however, is to provide exercise programs that are safe, effective, and attractive to the older population. The aim of this study was to investigate the short-term effect of a home-based exercise program with or without motivational interviewing (MI) compared with standard care on physical performance, fall self-efficacy, balance, activity level, handgrip strength, adherence to the exercise, and fall frequency.

    METHOD: A total of 175 older adults participated in this randomized controlled study. They were randomly allocated for the Otago Exercise Program (OEP) (n = 61), OEP combined with MI (n = 58), or a control group (n = 56). The participants' mean age was 83 years. The recruitment period was from October 2012 to May 2015. Measurements of physical performance, fall self-efficacy, balance, activity level, handgrip strength, adherence to the exercise, and fall frequency were done before and 12 weeks after randomization.

    RESULTS AND DISCUSSION: A total of 161 participants were followed up, and there were no significant differences between groups after a period of 12 weeks of regular exercise. Within the OEP + MI group, physical performance, fall self-efficacy, physical activity level, and handgrip strength improved significantly; likewise, improved physical performance and fall self-efficacy were found in the control group. A corresponding difference did not occur in the OEP group. Adherence to the exercise was generally high in both exercise groups.

    CONCLUSION: In the short-term perspective, there were no benefits of an exercise program with or without MI regarding physical performance, fall self-efficacy, activity level, handgrip strength, adherence to the exercise, and fall frequency in comparison to a control group. However, some small effects occurred within the OEP + MI group, indicating that there may be some possible value in behavioral change support combined with exercise in older adults that requires further evaluation in both short- and long-term studies.

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