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  • 1.
    Herrera, Guadalupe
    et al.
    Univ Nacl Cordoba, Fac Ciencias Quim, Dept Farmacol, IFEC CONICET, Haya de la Torre & Medina Allende Ciudad Univ, RA-5000 Cordoba, Argentina.
    Calfa, Gaston
    Univ Nacl Cordoba, Fac Ciencias Quim, Dept Farmacol, IFEC CONICET, Haya de la Torre & Medina Allende Ciudad Univ, RA-5000 Cordoba, Argentina.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. Sechenov First Moscow State Med Univ, Inst Translat Med & Biotechnol, Moscow, Russia.
    Lasaga, Mercedes
    Inst Invest Biomed INBIOMED UBA CONICET, Fac Med, Buenos Aires, DF, Argentina.
    Scimonelli, Teresa
    Univ Nacl Cordoba, Fac Ciencias Quim, Dept Farmacol, IFEC CONICET, Haya de la Torre & Medina Allende Ciudad Univ, RA-5000 Cordoba, Argentina.
    Memory consolidation impairment induced by Interleukin-1 beta is associated with changes in hippocampal structural plasticity2019In: Behavioural Brain Research, ISSN 0166-4328, E-ISSN 1872-7549, Vol. 370, article id 111969Article in journal (Refereed)
    Abstract [en]

    Pro-inflammatory cytokines, particularly Interleukin-1 beta (IL-1 beta), can affect cognitive processes such as learning and memory. The aim of this study was to establish whether the effect of IL-1 beta on contextual fear memory is associated with changes in hippocampal structural plasticity. We also studied the effect of alpha-melanocyte-stimulating hormone (alpha-MSH), a potent anti-inflammatory and neuro-protective peptide. Different groups of animals were implanted bilaterally in dorsal hippocampus (DH). After recovery they were conditioned for contextual fear memory and received the different treatments (vehicle, IL-1 beta, alpha-MSH or IL-1 beta + alpha-MSH). Memory was assessed 24 hs after conditioning and immediately after rats were perfused for dendritic spine analysis. Our results show that local hippocampal administration of IL-1 beta just after memory encoding induced impairment in contextual memory and a reduction in the total density of CA1 hippocampal dendritic spines, particularly the mature ones. alpha-MSH administration reversed the IL-1 beta induced changes. The results suggest that neuro-inflammation induced by IL-1 beta interferes with experience-dependent structural plasticity in DH whereas alpha-MSH has a beneficial modulatory role in preventing this effect.

  • 2.
    Moulin, Thiago C.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. Leopoldo de Meis Institute of Medical Biochemistry, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; Brain Institute, Federal University of Rio Grande do Norte, Rio Grande do Norte, Brazil.
    Petiz, Lyvia L.
    Brain Institute, Federal University of Rio Grande do Norte, Rio Grande do Norte, Brazil.
    Rayêe, Danielle
    Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
    Winne, Jessica
    Brain Institute, Federal University of Rio Grande do Norte, Rio Grande do Norte, Brazil.
    Maia, Roberto G.
    Leopoldo de Meis Institute of Medical Biochemistry, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
    Lima da Cruz, Rafael V.
    Brain Institute, Federal University of Rio Grande do Norte, Rio Grande do Norte, Brazil.
    Amaral, Olavo B.
    Leopoldo de Meis Institute of Medical Biochemistry, Federal University of Rio de Janeiro, Rio de Janeiro, Brazi.
    Leão, Richardson N.
    Brain Institute, Federal University of Rio Grande do Norte, Rio Grande do Norte, Brazil.
    Chronic in vivo optogenetic stimulation modulates neuronal excitability, spine morphology, and Hebbian plasticity in the mouse hippocampus2019In: Hippocampus, ISSN 1050-9631, E-ISSN 1098-1063, Vol. 29, no 8, p. 755-761Article in journal (Refereed)
    Abstract [en]

    Prolonged increases in excitation can trigger cell‐wide homeostatic responses in neurons, altering membrane channels, promoting morphological changes, and ultimately reducing synaptic weights. However, how synaptic downscaling interacts with classical forms of Hebbian plasticity is still unclear. In this study, we investigated whether chronic optogenetic stimulation of hippocampus CA1 pyramidal neurons in freely moving mice could (a) cause morphological changes reminiscent of homeostatic scaling, (b) modulate synaptic currents that might compensate for chronic excitation, and (c) lead to alterations in Hebbian plasticity. After 24 hr of stimulation with 15‐ms blue light pulses every 90 s, dendritic spine density and area were reduced in the CA1 region of mice expressing channelrhodopsin‐2 (ChR2) when compared to controls. This protocol also reduced the amplitude of mEPSCs for both the AMPA and NMDA components in ex vivo slices obtained from ChR2‐expressing mice immediately after the end of stimulation. Finally, chronic stimulation impaired the induction of LTP and facilitated that of LTD in these slices. Our results indicate that neuronal responses to prolonged network excitation can modulate subsequent Hebbian plasticity in the hippocampus.

  • 3.
    Olivo, Gaia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Zhukovsky, Christina
    Salonen-Ros, Helena
    Larsson, Elna-Marie
    Brooks, Samantha
    Schiöth, Helgi
    Functional connectivity underlying hedonic response to food in female adolescents with atypical AN: The role of somatosensory and salience networksManuscript (preprint) (Other academic)
    Abstract [en]

    Atypical Anorexia Nervosa (AN) usually occurs during adolescence. Patients are often in the normal-weight range at diagnosis, however they often present with signs of medical complications and severe restraint over eating, body dissatisfaction, and low self-esteem. We investigated functional circuitry underlying the hedonic response in 28 female adolescent patients diagnosed with atypical AN and 33 healthy controls. Participants were shown images of food with high (HC) or low (LC) caloric content in alternating blocks during functional MRI. The HC > LC contrast was calculated. Based on previous literature on full-threshold AN, we hypothesized that patients would exhibit increased connectivity in areas involved in sensory processing and bottom-up responses, coupled to increased connectivity from areas related to top-down inhibitory control, compared with controls. Patients showed increased connectivity in pathways related to multimodal somatosensory processing and memory retrieval. The connectivity was on the other hand decreased in patients in salience and attentional networks, and in a wide cerebello-occipital network. Our study was the first investigation of food-related neural response in atypical AN. Our findings support higher somatosensory processing in patients in response to HC food images compared with controls, however HC food was less efficient than LC food in engaging patients’ bottom-up salient responses, and was not associated with connectivity increases in inhibitory control regions. These findings suggest that the psychopathological mechanisms underlying food restriction in atypical AN differ from full-threshold AN. Elucidating the mechanisms underlying the development and maintenance of eating behaviour in atypical AN might help designing specific treatment strategies.

  • 4.
    Pisanu, Claudia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. Univ Cagliari, Sect Neurosci & Clin Pharmacol, Dept Biomed Sci, Cagliari, Italy.
    Squassina, Alessio
    Univ Cagliari, Sect Neurosci & Clin Pharmacol, Dept Biomed Sci, Cagliari, Italy;Dalhousie Univ, Dept Psychiat, Halifax, NS, Canada.
    Treatment-Resistant Schizophrenia: Insights From Genetic Studies and Machine Learning Approaches2019In: Frontiers in Pharmacology, ISSN 1663-9812, E-ISSN 1663-9812, Vol. 10, article id 617Article, review/survey (Refereed)
    Abstract [en]

    Schizophrenia (SCZ) is a severe psychiatric disorder affecting approximately 23 million people worldwide. It is considered the eighth leading cause of disability according to the Wood Health Organization and is associated with a significant reduction in life expectancy. Antipsychotics represent the first-choice treatment in SCZ, but approximately 30% of patients fail to respond to acute treatment. These patients are generally defined as treatment-resistant and are eligible for clozapine treatment. Treatment-resistant patients show a more severe course of the disease, but it has been suggested that treatment-resistant schizophrenia (TRS) may constitute a distinct phenotype that is more than just a more severe form of SCZ. TRS is heritable, and genetics has been shown to play an important role in modulating response to antipsychotics. Important efforts have been put into place in order to better understand the genetic architecture of TRS, with the main goal of identifying reliable predictive markers that might improve the management and quality of life of TRS patients. However, the number of candidate gene and genome-wide association studies specifically focused on TRS is limited, and to date, findings do not allow the disentanglement of its polygenic nature. More recent studies implemented polygenic risk score, gene-based and machine learning methods to explore the genetics of TRS, reporting promising findings. In this review, we present an overview on the genetics of TRS, particularly focusing our discussion on studies implementing polygenic approaches.

  • 5.
    Tan, Xiao
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    van Egmond, Lieve
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Partinen, Markku
    Univ Helsinki, Dept Neurol Sci, Helsinki, Finland;Helsinki Sleep Clin, VitalMed Res Ctr, Helsinki, Finland.
    Lange, Tanja
    Univ Lubeck, Dept Rheumatol & Clin Immunol, Lubeck, Germany.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    A narrative review of interventions for improving sleep and reducing circadian disruption in medical inpatients2019In: Sleep Medicine, ISSN 1389-9457, E-ISSN 1878-5506, Vol. 59, p. 42-50Article, review/survey (Refereed)
    Abstract [en]

    Sleep and circadian disruptions are frequently observed in patients across hospital wards. This is alarming, since impaired nocturnal sleep and disruption of a normal circadian rhythm can compromise health and disturb processes involved in recovery from illness (eg, immune functions). With this in mind, the present narrative review discusses how patient characteristics (sleep disorders, anxiety, stress, chronotype, and disease), hospital routines (pain management, timing of medication, nocturnal vital sign monitoring, and physical inactivity), and hospital environment (light and noise) may all contribute to sleep disturbances and circadian misalignment in patients. We also propose hospital-based strategies that may help reduce sleep and circadian disruptions in patients admitted to the hospital. (C) 2018 The Authors. Published by Elsevier B.V.

  • 6.
    Tan, Xiao
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    van Egmond, Lieve
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Partinen, Markku
    Univ Helsinki, Dept Neurol Sci, Helsinki, Finland.
    Lange, Tanja
    Helsinki Sleep Clin, VitalMed Res Ctr, Helsinki, Finland.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Response to comment on "A narrative review of interventions for improving sleep and reducing circadian disruption in medical inpatients"2019In: Sleep Medicine, ISSN 1389-9457, E-ISSN 1878-5506, Vol. 59, p. 53-53Article in journal (Other academic)
  • 7.
    van Egmond, Lieve
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Tan, Xiao
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Sjögren, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Association between Healthy Dietary Patterns and Self-Reported Sleep Disturbances in Older Men: The ULSAM Study2019In: Nutrients, ISSN 2072-6643, E-ISSN 2072-6643, Vol. 11, no 5, article id 1029Article in journal (Refereed)
    Abstract [en]

    To date, little is known about how dietary patterns may link to measures of sleep quality in older subjects, who often suffer from sleep problems. Here, we investigated, in an older male population from Sweden (n = 970; aged 71 +/- 1 year), whether adherence to the Healthy Diet Indicator (HDI; based on recommendations from the World Health Organization) or the Mediterranean Diet (MD) is linked to sleep disturbances. The diet scores were calculated using a seven-day food diary, and self-reported sleep initiation or maintenance problems were assessed by questionnaires. When adjusted for potential confounders, no associations between dietary scores and sleep parameters were found. In contrast, low consumption of milk and dairy products one of the dietary features of the MD was associated with better subjective sleep initiation. This association was, however, not found in men with adequate reports of daily energy intake (similar to 54% of the cohort). To summarize, our findings do not suggest that older men can mitigate perceived difficulties to fall and stay asleep by adhering to either the HDI or MD. Whether low consumption of milk and dairy products can facilitate sleep initiation must be confirmed in future studies by utilizing objective measures of sleep such as polysomnography. Finally, when investigating associations between dietary patterns and sleep, particular attention should be paid to the potential confounder of inadequate reporting of energy intake.

  • 8.
    Wang, Ludi
    et al.
    Beijing Univ Posts & Telecommun, Automat Sch, Beijing 100876, Peoples R China.
    Zhou, Wei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Chang, Qing
    Shanghai Univ Med & Hlth Sci, Jiading Dist Cent Hosp, Shanghai Gen Practice Med Educ & Res Ctr, Shanghai 201800, Peoples R China.
    Chen, Jiangen
    Jiading Ind Dist Community Hlth Serv Ctr, Dept Gen Med, Shanghai 201800, Peoples R China.
    Zhou, Xiaoguang
    Beijing Univ Posts & Telecommun, Automat Sch, Beijing 100876, Peoples R China;Minjiang Univ, Sch Econ & Management, Fuzhou 350108, Fujian, Peoples R China.
    Deep Ensemble Detection of Congestive Heart Failure Using Short-Term RR Intervals2019In: IEEE Access, E-ISSN 2169-3536, Vol. 7, p. 69559-69574Article in journal (Refereed)
    Abstract [en]

    Heart rate variability (HRV) is an effective predictor of congestive heart failure (CHF). However, important challenges exist regarding the effective temporal feature extraction and efficient classification using high-dimensional HRV representations. To solve these challenges, an ensemble method for CHF detection using short-term HRV data and deep neural networks was proposed. In this paper, five opensource databases, the BIDMC CHF database (BIDMC-CHF), CHF RR interval database (CHF-RR), MITBIH normal sinus rhythm (NSR) database, fantasia database (ED), and NSR RR interval database (NSR-RR), were used. Additionally, three RR segment length types (N = 500, 1000, and 2000) were used to evaluate the proposed method. First, we extracted the expert features of RR intervals (RRIs) and then built a long short-term memory-convolutional neural network-based network to extract deep-learning (DL) features automatically. Finally, an ensemble classifier was used for CHF detection using the above features. With blindfold validation (three CHF subjects and three normal subjects), the proposed method achieved 99.85%, 99.41%, and 99.17% accuracy on N = 500, 1000, and 2000 length RRIs, respectively, using the BIDMC-CHF, NSR, and FD databases. With blindfold validation (six CHF subjects and six normal subjects), the proposed method achieved 83.84%, 87.54%, and 85.71% accuracy on N = 500, 1000, and 2000 length RRIs, respectively, using the NSR-RR and CHF-RR ndatabases. Based on feature ranking, the significant effectiveness provided by the DL features has been proven. The results have shown that the deep ensemble method can achieve reliable CHF detection using short-term heart rate signals and enable CHF detection through intelligent hardware.

  • 9.
    Wang, Lu-di
    et al.
    Beijing Univ Posts & Telecommun, Automat Sch, Beijing 100876, Peoples R China.
    Zhou, Wei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.
    Xing, Ying
    Beijing Univ Posts & Telecommun, Automat Sch, Beijing 100876, Peoples R China.
    Liu, Na
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Movahedipour, Mahmood
    Beijing Univ Posts & Telecommun, Sch Econ & Management, Beijing 100876, Peoples R China;ACECR, Tehran 141554364, Iran.
    Zhou, Xiao-guang
    Beijing Univ Posts & Telecommun, Automat Sch, Beijing 100876, Peoples R China.
    A novel method based on convolutional neural networks for deriving standard 12-lead ECG from serial 3-lead ECG2019In: FRONTIERS OF INFORMATION TECHNOLOGY & ELECTRONIC ENGINEERING, ISSN 2095-9184, Vol. 20, no 3, p. 405-413Article in journal (Refereed)
    Abstract [en]

    Reconstruction of a 12-lead electrocardiogram (ECG) from a serial 3-lead ECG has been researched in the past to satisfy the need for more wearing comfort and ambulatory situations. The accuracy and real-time performance of traditional methods need to be improved. In this study, we present a novel method based on convolutional neural networks (CNNs) for the synthesis of missing precordial leads. The results show that the proposed method receives better similarity and consumes less time using the PTB database. Particularly, the presented method shows outstanding performance in reconstructing the pathological ECG signal, which is crucial for cardiac diagnosis. Our CNN-based method is shown to be more accurate and time-saving for deployment in non-hospital situations to synthesize a standard 12-lead ECG from a reduced lead-set ECG recording. This is promising for real cardiac care.

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