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  • 1.
    Bazov, Igor
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Sarkisyan, Daniil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Kononenko, Olga
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Watanabe, Hiroyuki
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Taqi, Malik Mumtaz
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Faculty of Medicine, NORMENT, University of Oslo, Oslo, Norway.
    Stålhandske, Lada
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Verbeek, Dineke S
    Department of Genetics, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.
    Mulder, Jan
    Department of Neuroscience, Science for Life Laboratory, Karolinska Institute, Stockholm, Sweden.
    Rajkowska, Grazyna
    Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS, USA.
    Sheedy, Donna
    Discipline of Pathology, Sydney Medical School, University of Sydney, Sydney NSW, Australia.
    Kril, Jillian
    Discipline of Pathology, Sydney Medical School, University of Sydney, Sydney NSW, Australia.
    Sun, Xueguang
    Zymo Research Corporation, 17062 Murphy Avenue, Irvine, CA, USA; Division of Human Genetics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA.
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Yakovleva, Tatiana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Bakalkin, Georgy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Neuronal Expression of Opioid Gene is Controlled by Dual Epigenetic and Transcriptional Mechanism in Human Brain2018In: Cerebral Cortex, ISSN 1047-3211, E-ISSN 1460-2199, Vol. 28, no 9, p. 3129-3142Article in journal (Refereed)
    Abstract [en]

    Molecular mechanisms that define patterns of neuropeptide expression are essential for the formation and rewiring of neural circuits. The prodynorphin gene (PDYN) gives rise to dynorphin opioid peptides mediating depression and substance dependence. We here demonstrated that PDYN is expressed in neurons in human dorsolateral prefrontal cortex (dlPFC), and identified neuronal differentially methylated region in PDYN locus framed by CCCTC-binding factor binding sites. A short, nucleosome size human-specific promoter CpG island (CGI), a core of this region may serve as a regulatory module, which is hypomethylated in neurons, enriched in 5-hydroxymethylcytosine, and targeted by USF2, a methylation-sensitive E-box transcription factor (TF). USF2 activates PDYN transcription in model systems, and binds to nonmethylated CGI in dlPFC. USF2 and PDYN expression is correlated, and USF2 and PDYN proteins are co-localized in dlPFC. Segregation of activatory TF and repressive CGI methylation may ensure contrasting PDYN expression in neurons and glia in human brain.

  • 2. Boyle, Julie A.
    et al.
    Djordjevic, Jelena
    Olsson, Mats J.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Lundström, Johan N.
    Jones-Gotman, Marilyn
    The Human Brain Distinguishes between Single Odorants and Binary Mixtures2009In: Cerebral Cortex, ISSN 1047-3211, E-ISSN 1460-2199, Vol. 19, no 1, p. 66-71Article in journal (Refereed)
    Abstract [en]

    Single odors are processed differently from odor mixtures in the cortex of rodents. We investigated whether single and binary odor mixtures activate different regions also in the human brain. We analyzed data from positron emission tomography scans using pyridine, citral, and 5 mixtures of pyridine and citral in proportions varying from 10/90 to 90/10, with 50/50 being the most impure. Comparing mixtures with single odorants gave activation in the left cingulate and right parietal and superior frontal cortices and bilateral activation in the anterior and lateral orbitofrontal cortices. We also found that brain activity in the lateral orbitofrontal cortex (OFC) increased with odorant impurity, whereas the anterior OFC was activated for binary odor mixtures and deactivated for single components. We conclude that binary odor mixtures and their individual components are processed differently by the human brain. The lateral portion of the OFC responds to mixture impurity in a graded fashion, whereas the anterior portion acts like an on-off detector of odor mixtures.

  • 3.
    Mueller, Christian P.
    et al.
    Friedrich Alexander Univ Erlangen Nuremberg, Univ Clin, Dept Psychiat & Psychotherapy, Sect Addict Med, Schwabachanlage 6, D-91054 Erlangen, Germany.
    Chu, Congying
    Kings Coll London, Inst Psychiat Psychol & Neurosci, Ctr Populat Neurosci & Stratified Med PONS, De Crespigny Pk, London SE5 8AF, England;Kings Coll London, Inst Psychiat Psychol & Neurosci, MRC SGDP Ctr, De Crespigny Pk, London SE5 8AF, England.
    Qin, Liya
    Univ N Carolina, Sch Med, Bowles Ctr Alcohol Studies, Chapel Hill, NC 27599 USA.
    Liu, Chunyu
    Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA;NHLBI, Populat Sci Branch, Div Intramural Res, Bethesda, MD 20824 USA;Boston Univ, Sch Publ Hlth, 715 Albany St, Boston, MA 02118 USA.
    Xu, Bing
    Kings Coll London, Inst Psychiat Psychol & Neurosci, Ctr Populat Neurosci & Stratified Med PONS, De Crespigny Pk, London SE5 8AF, England;Kings Coll London, Inst Psychiat Psychol & Neurosci, MRC SGDP Ctr, De Crespigny Pk, London SE5 8AF, England.
    Gao, He
    Imperial Coll London, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, Dept Epidemiol & Biostat, London W2 1PG, England.
    Ruggeri, Barbara
    Kings Coll London, Inst Psychiat Psychol & Neurosci, Ctr Populat Neurosci & Stratified Med PONS, De Crespigny Pk, London SE5 8AF, England;Kings Coll London, Inst Psychiat Psychol & Neurosci, MRC SGDP Ctr, De Crespigny Pk, London SE5 8AF, England.
    Hieber, Saskia
    Friedrich Alexander Univ Erlangen Nuremberg, Univ Clin, Dept Psychiat & Psychotherapy, Sect Addict Med, Schwabachanlage 6, D-91054 Erlangen, Germany.
    Schneider, Julia
    Friedrich Alexander Univ Erlangen Nuremberg, Inst Biochem & Mol Med, Fahrstr 17, D-91054 Erlangen, Germany.
    Jia, Tianye
    Kings Coll London, Inst Psychiat Psychol & Neurosci, Ctr Populat Neurosci & Stratified Med PONS, De Crespigny Pk, London SE5 8AF, England;Kings Coll London, Inst Psychiat Psychol & Neurosci, MRC SGDP Ctr, De Crespigny Pk, London SE5 8AF, England.
    Tay, Nicole
    Kings Coll London, Inst Psychiat Psychol & Neurosci, Ctr Populat Neurosci & Stratified Med PONS, De Crespigny Pk, London SE5 8AF, England;Kings Coll London, Inst Psychiat Psychol & Neurosci, MRC SGDP Ctr, De Crespigny Pk, London SE5 8AF, England.
    Akira, Shizuo
    Osaka Univ, Microbial Dis Res Inst, World Premier Int Immunol Frontiern Res Ctr, Lab Host Def, 1-1 Yamadaoka, Suita, Osaka 5650871, Japan.
    Satoh, Takashi
    Osaka Univ, Microbial Dis Res Inst, World Premier Int Immunol Frontiern Res Ctr, Lab Host Def, 1-1 Yamadaoka, Suita, Osaka 5650871, Japan.
    Banaschewski, Tobias
    Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Child & Adolescent Psychiat & Psychotherapy, J5, D-68159 Mannheim, Germany.
    Bokde, Arun L. W.
    Trinity Coll Dublin, Sch Med, Discipline Psychiat, Jamess St, Dublin 8, Ireland;Trinity Coll Dublin, Trin Coll Inst Neurosci, Jamess St, Dublin 8, Ireland.
    Bromberg, Uli
    Univ Med Ctr Hamburg Eppendorf, House W34,3 OG,Martinistr 52, D-20246 Hamburg, Germany.
    Buechel, Christian
    Univ Med Ctr Hamburg Eppendorf, House W34,3 OG,Martinistr 52, D-20246 Hamburg, Germany.
    Quinlan, Erin Burke
    Kings Coll London, Inst Psychiat Psychol & Neurosci, Ctr Populat Neurosci & Stratified Med PONS, De Crespigny Pk, London SE5 8AF, England;Kings Coll London, Inst Psychiat Psychol & Neurosci, MRC SGDP Ctr, De Crespigny Pk, London SE5 8AF, England.
    Flor, Herta
    Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Cognit & Clin Neurosci, J5, D-68159 Mannheim, Germany;Univ Mannheim, Sch Social Sci, Dept Psychol, D-68131 Mannheim, Germany.
    Frouin, Vincent
    Univ Paris Saclay, CEA, NeuroSpin, F-91191 Gif Sur Yvette, France.
    Garavan, Hugh
    Univ Vermont, Dept Psychiat, Burlington, VT 05405 USA;Univ Vermont, Dept Psychol, Burlington, VT 05405 USA.
    Gowland, Penny
    Univ Nottingham, Sch Phys & Astron, Sir Peter Mansfield Imaging Ctr, Univ Pk, Nottingham NG7 2QX, England.
    Heinz, Andreas
    Charite Univ Med Berlin, Campus Charite Mitte, Dept Psychiat & Psychotherapy, Charitepl 1, D-10117 Berlin, Germany.
    Ittermann, Bernd
    PTB, Braunschweig, Germany;PTB, Abbestr 2-12, D-10587 Berlin, Germany.
    Martinot, Jean-Luc
    Univ Paris Saclay, Univ Paris Sud, INSERM, Unit 1000,Neuroimaging & Psychiat,DIGITEO Labs, Rue Noetzlin, F-91190 Gif Sur Yvette, France.
    Martinot, Marie-Laure Paillere
    Univ Paris Saclay, Univ Paris Sud, INSERM, Unit 1000,Neuroimaging & Psychiat, Gif Sur Yvette, France;Hop La Pitie Salpetriere, AP HP, Dept Child & Adolescent Psychiat, 47-83 Blvd Hop, F-75013 Paris, France.
    Artiges, Eric
    Univ Paris Saclay, Univ Paris Sud, INSERM, Unit 1000,Neuroimaging & Psychiat,DIGITEO Labs, Rue Noetzlin, F-91190 Gif Sur Yvette, France;Orsay Hosp, Psychiat Dept 91G16, Orsay, France.
    Lemaitre, Herve
    Univ Paris Sud, Sch Med, INSERM, Unit 1000,Neuroimaging & Psychiat, Gif Sur Yvette, France.
    Nees, Frauke
    Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Child & Adolescent Psychiat & Psychotherapy, J5, D-68159 Mannheim, Germany;Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Cognit & Clin Neurosci, J5, D-68159 Mannheim, Germany.
    Orfanos, Dimitri Papadopoulos
    Univ Paris Saclay, CEA, NeuroSpin, F-91191 Gif Sur Yvette, France.
    Paus, Tomas
    Univ Toronto, Rotman Res Inst, 3560 Bathurst St, Toronto, ON M6A 2E1, Canada;Univ Toronto, Dept Psychol, 3560 Bathurst St, Toronto, ON M6A 2E1, Canada;Univ Toronto, Dept Psychiat, 3560 Bathurst St, Toronto, ON M6A 2E1, Canada.
    Poustka, Luise
    Univ Med Ctr Gottingen, Dept Child & Adolescent Psychiat & Psychotherapy, von Siebold Str 5, D-37075 Gottingen, Germany;Med Univ Vienna, Clin Child & Adolescent Psychiat, Wahringer Gurtel 18-20, A-1090 Vienna, Austria.
    Millenet, Sabina
    Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Child & Adolescent Psychiat & Psychotherapy, J5, D-68159 Mannheim, Germany.
    Froehner, Juliane H.
    Tech Univ Dresden, Dept Psychiat, Chemnitzer Str 46a, D-01187 Dresden, Germany;Tech Univ Dresden, Neuroimaging Ctr, Chemnitzer Str 46a, D-01187 Dresden, Germany.
    Smolka, Michael N.
    Tech Univ Dresden, Dept Psychiat, Chemnitzer Str 46a, D-01187 Dresden, Germany;Tech Univ Dresden, Neuroimaging Ctr, Chemnitzer Str 46a, D-01187 Dresden, Germany.
    Walter, Henrik
    Charite Univ Med Berlin, Campus Charite Mitte, Dept Psychiat & Psychotherapy, Charitepl 1, D-10117 Berlin, Germany.
    Whelan, Robert
    Aras Phiarsaigh Trinity Coll Dublin, Sch Psychol, Dublin 2, Ireland;Aras Phiarsaigh Trinity Coll Dublin, Global Brain Hlth Inst, Dublin 2, Ireland.
    Bakalkin, Georgy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Liu, Yun
    Minist Educ, Key Lab Metab & Mol Med, Shanghai, Peoples R China;Fudan Univ, Shanghai Med Coll, Dept Biochem & Mol Biol, Shanghai, Peoples R China.
    Desrivieres, Sylvane
    Kings Coll London, Inst Psychiat Psychol & Neurosci, Ctr Populat Neurosci & Stratified Med PONS, De Crespigny Pk, London SE5 8AF, England;Kings Coll London, Inst Psychiat Psychol & Neurosci, MRC SGDP Ctr, De Crespigny Pk, London SE5 8AF, England.
    Elliott, Paul
    Imperial Coll London, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, Dept Epidemiol & Biostat, London W2 1PG, England.
    Eulenburg, Volker
    Friedrich Alexander Univ Erlangen Nuremberg, Inst Biochem & Mol Med, Fahrstr 17, D-91054 Erlangen, Germany;Univ Leipzig, Dept Anaesthesiol & Intens Care Med, Liebigstr 20, D-04103 Leipzig, Germany.
    Levy, Daniel
    Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA;NHLBI, Populat Sci Branch, Div Intramural Res, Bethesda, MD 20824 USA.
    Crews, Fulton
    Univ N Carolina, Sch Med, Bowles Ctr Alcohol Studies, Chapel Hill, NC 27599 USA.
    Schumann, Gunter
    Kings Coll London, Inst Psychiat Psychol & Neurosci, Ctr Populat Neurosci & Stratified Med PONS, De Crespigny Pk, London SE5 8AF, England;Kings Coll London, Inst Psychiat Psychol & Neurosci, MRC SGDP Ctr, De Crespigny Pk, London SE5 8AF, England.
    The Cortical Neuroimmune Regulator TANK Affects Emotional Processing and Enhances Alcohol Drinking: A Translational Study2019In: Cerebral Cortex, ISSN 1047-3211, E-ISSN 1460-2199, Vol. 29, no 4, p. 1736-1751Article in journal (Refereed)
    Abstract [en]

    Alcohol abuse is a major public health problem worldwide. Understanding the molecular mechanisms that control regular drinking may help to reduce hazards of alcohol consumption. While immunological mechanisms have been related to alcohol drinking, most studies reported changes in immune function that are secondary to alcohol use. In this report, we analyse how the gene "TRAF family member-associated NF-kappa B activator" (TANK) affects alcohol drinking behavior. Based on our recent discovery in a large GWAS dataset that suggested an association of TANK, SNP rs197273, with alcohol drinking, we report that SNP rs197273 in TANK is associated both with gene expression (P = 1.16 x 10(-19)) and regional methylation (P = 5.90 x 10(-25)). A tank knock out mouse model suggests a role of TANK in alcohol drinking, anxiety-related behavior, as well as alcohol exposure induced activation of insular cortex NF-kappa B. Functional and structural neuroimaging studies among up to 1896 adolescents reveal that TANK is involved in the control of brain activity in areas of aversive interoceptive processing, including the insular cortex, but not in areas related to reinforcement, reward processing or impulsiveness. Our findings suggest that the cortical neuroimmune regulator TANK is associated with enhanced aversive emotional processing that better protects from the establishment of alcohol drinking behavior.

  • 4.
    Watanabe, Hiroyuki
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Fitting, Sylvia
    Hussain, Muhammad
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Kononenko, Olga
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Iatsyshyna, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Yoshitake, Takashi
    Kehr, Jan
    Alkass, Kanar
    Druid, Henrik
    Wadensten, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Andren, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Nylander, Ingrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Wedell, Douglas
    Krishtal, Oleg
    Hauser, Kurt
    Nyberg, Fred
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Karpyak, Victor
    Yakovleva, Tatjana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Bakalkin, Georgy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Asymmetry of the Endogenous Opioid System in the Human Anterior Cingulate: a Putative Molecular Basis for Lateralization of Emotions and Pain2015In: Cerebral Cortex, ISSN 1047-3211, E-ISSN 1460-2199, Vol. 25, no 1, p. 97-108Article in journal (Refereed)
    Abstract [en]

    Lateralization of processing of positive and negative emotions and pain suggests an asymmetric distribution of the neurotransmitter systems regulating these functions between the left and right brain hemispheres. By virtue of their ability to selectively mediate euphoria, dysphoria and pain, the m-, d- and k-opioid receptors and their endogenous ligands may subserve these lateralized functions. We addressed this hypothesis by comparing the levels of the opioid receptors and peptides in the left and right anterior cingulate cortex (ACC), a key area for emotion and pain processing. Opioid mRNAs and peptides and five “classical” neurotransmitters were analyzed in postmortem tissues from 20 human subjects. Leu-enkephalin-Arg and Met-enkephalin-Arg-Phe, preferential d-/m- and k-/m-opioid agonists demonstrated marked lateralization to the left and right ACC, respectively. Dynorphin B strongly correlated with Leu-enkephalin-Arg in the left but not right ACC suggesting different mechanisms of conversion of this k-opioid agonist to d-/m-opioid ligand in the two hemispheres; in the right ACC dynorphin B may be cleaved by PACE4, a proprotein convertase regulating left-right asymmetry formation. These findings suggest that region-specific lateralization of neuronal networks expressing opioid peptides underlyes in part lateralization of higher functions including positive and negative emotions and pain in the human brain.

1 - 4 of 4
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