Developmental Neurosciences
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The Critical Importance of Basic Animal Research for Neuropsychiatric Disorders
The critical importance of basic animal research for neuropsychiatric disorders Tracy L. Bale1, Ted Abel2, Huda Akil3, William A. Carlezon4, Bita Moghaddam5, Eric J. Nestler6, Kerry J. Ressler7 and Scott M. Thompson8 1 Center for Epigenetic Research in Child Health and Brain Development, Departments of Pharmacology and Psychiatry, University of Maryland School of Medicine, Baltimore, MD, [email protected] 2 Department of Pharmacology and Iowa Neuroscience Institute, Carver College of Medicine, University of Iowa, Iowa City, IA, [email protected] 3 Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, [email protected] 4 McLean Hospital, Department of Psychiatry, Harvard School of Medicine, Belmont, MA, [email protected] 5 Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR, [email protected] 6 Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, [email protected] 7 McLean Hospital, Department of Psychiatry, Harvard School of Medicine, Belmont, MA, [email protected] 8 Department of Physiology, University of Maryland School of Medicine, Baltimore, MD, [email protected] Contact information: Tracy L. Bale, Ph.D. Professor and Director, Center for Epigenetic Research in Child Health and Brain Development Departments of Pharmacology and Psychiatry University of Maryland School of Medicine, Baltimore, MD 21201 [email protected] ph 410-706-5816 Acknowledgements: Authors acknowledge support funding from NIMH grants: MH104184, MH108286, MH099910 (TLB); MH086828 (SMT); MH048404, MH115027 (BM), MH063266 (WAC), MH108665, MH110441, MH110925, MH117292 (KJR); MH051399, MH096890 (EJN), MH104261 (HA), MH087463, MH117964 (TA). The challenges and critical importance of keeping our thinking about neuropsychiatric disorders mechanisms and classifications up-to-date have prompted a dynamic discourse as to the value, appropriateness, and reliability of the animal models we use and the outcomes we measure. -
Uneven Balance of Power Between Hypothalamic Peptidergic Neurons in the Control of Feeding
Uneven balance of power between hypothalamic peptidergic neurons in the control of feeding Qiang Weia, David M. Krolewskia, Shannon Moorea, Vivek Kumara, Fei Lia, Brian Martina, Raju Tomerb, Geoffrey G. Murphya, Karl Deisserothc, Stanley J. Watson Jr.a, and Huda Akila,1 aMolecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI 48109; bDepartment of Biological Sciences, Columbia University, New York, NY 10027; and cDepartment of Bioengineering, Stanford University, Stanford, CA 94305 Contributed by Huda Akil, August 7, 2018 (sent for review February 6, 2018; reviewed by Olivier Civelli and Allen Stuart Levine) Two classes of peptide-producing neurons in the arcuate nucleus consumption, while anorexigenic neurons that express POMC in- (Arc) of the hypothalamus are known to exert opposing actions on hibit feeding behavior. AgRP/NPY neurons are active when the feeding: the anorexigenic neurons that express proopiomelano- energy stores are not sufficient to meet systemic demands, thereby cortin (POMC) and the orexigenic neurons that express agouti- releasing AgRP and promoting feeding (9, 10). POMC is a complex related protein (AgRP) and neuropeptide Y (NPY). These neurons polypeptide precursor cleaved into active peptides including mel- are thought to arise from a common embryonic progenitor, but anocortins and β-endorphin (11). While β-endorphin is a long- our anatomical and functional understanding of the interplay of acting opioid analgesic (12), the cosynthesized α-melanocyte stim- these two peptidergic systems that contribute to the control of ulating hormone (α-MSH) blocks appetite (13). These two sets of feeding remains incomplete. The present study uses a combination peptidergic neurons in the Arc respond to nutrient and hormonal of optogenetic stimulation with viral and transgenic approaches, signals from the periphery. -
Huda Akil, Ph.D
Huda Akil, Ph.D. is the Gardner Quarton Distinguished University Professor of Neuroscience and Psychiatry and the co-Director of the Molecular & Behavioral Neuroscience Institute (MBNI) at the University of Michigan. Dr. Akil and her colleagues have made seminal contributions to the understanding of the brain biology of emotions, including pain, stress, anxiety and substance abuse. Her current research investigates the genetic and neural mechanisms underlying addiction and mood disorders. Among her contributions, Dr. Akil provided the first physiological evidence for a role of endorphins in the brain, and showed that endorphins are activated by stress and cause pain inhibition. Her laboratory has developed new genetic animal models of temperament and shown their relevance to human disorders, including addiction and depression. She is a member of the Pritzker Consortium, which is engaged in large-scale studies to discover new genes and proteins that cause vulnerability to major depression and bipolar illness. Her work has uncovered the role of the Fibroblast Growth Factor (FGF) family in depression, anxiety and established its functions in the development and control of emotions. Dr. Akil has served on several national and international organizations to promote scientific and brain health awareness nationally and globally. She is the past President of the American College of Neuropsychopharmacology (1998) and the past President of the Society for Neuroscience (2004) the largest neuroscience organization in the world. She has served two terms on the Council of the National Academy of Medicine and served on the National Research Council (NRC) review board. Dr. Akil’s contributions have been recognized with numerous honors and awards, including honorary doctorates. -
KAFUI DZIRASA, MD Phd
KAFUI DZIRASA, MD PhD 421 Bryan Research, Box 3209 E-mail: [email protected] 311 Research Drive Durham, North Carolina 27710 Duke University Medical Center Office: (919) 681-7371 EDUCATION: University of Maryland Baltimore County, Baltimore, MD June 1996-May 2001 Bachelor of Science in Chemical Engineering, Magna cum laude Meyerhoff Scholar Duke University Graduate School, Durham NC August 2003-March 2007 Doctor of Philosophy in Neurobiology Thesis: Electrophysiological Correlates of Neurological and Psychiatric Disease Advisor: Miguel Nicolelis Postdoctoral Research August 2007-March 2009 Duke University, Durham, NC Advisor: Miguel Nicolelis Duke University School of Medicine, Durham, NC August 2001-May 2009 Doctor of Medicine Medical Scientist Training Program Duke University Hospital, Durham, NC July 2010-June 2016 Residency, General Psychiatry North Carolina Medical License License #: 2016-02599 License Status: Active EMPLOYMENT HISTORY: K. Ranga Rama Krishnan Endowed Associate Professor with Tenure, Department of Psychiatry and Behavioral Sciences. Duke University Medical Center. Aug 2019-Current K. Ranga Rama Krishnan Endowed Associate Professor, Tenure Track, Department of Psychiatry and Behavioral Sciences. Duke University Medical Center. May 2018-July 2019 Associate Professor, Tenure Track, Department of Psychiatry and Behavioral Sciences. Duke University Medical Center. September 2017-May 2018 Assistant Professor, Tenure Track, Department of Psychiatry and Behavioral Sciences. Duke University Medical Center. December 2013-August 2017 Assistant Research Professor, Department of Neurobiology. Duke University. October 2012-Current. Assistant Professor, Department of Biomedical Engineering. Duke University. March 2012-Current. Visiting Professor of Neuroscience, Edmond and Lily Safra International Institute of Neurosciences of Natal (ELS-IINN). August 2011-2019. General Psychiatry Resident, Department of Psychiatry and Behavioral Sciences. -
WAVE1 in Neurons Expressing the D1 Dopamine Receptor Regulates Cellular and Behavioral Actions of Cocaine
WAVE1 in neurons expressing the D1 dopamine receptor regulates cellular and behavioral actions of cocaine Ilaria Cegliaa,1, Ko-Woon Leea,1, Michael E. Cahillb,1, Steven M. Gravesc, David Dietzd, Dalton J. Surmeierc, Eric J. Nestlerb, Angus C. Nairna,e, Paul Greengarda,2, and Yong Kima,2 aLaboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10065; bFishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029; cDepartment of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611; dDepartment of Pharmacology and Toxicology, Research Institute on Addictions, Program in Neuroscience, State University of New York at Buffalo, Buffalo, NY 14214; and eDepartment of Psychiatry, Yale University School of Medicine, New Haven, CT 06508 Contributed by Paul Greengard, December 23, 2016 (sent for review October 26, 2016; reviewed by Huda Akil and Solomon H. Snyder) Wiskott-Aldrich syndrome protein (WASP) family verprolin homolo- upon stimulation of D1 dopamine and of NMDA glutamate re- + gous protein 1 (WAVE1) regulates actin-related protein 2/3 (Arp2/3) ceptors, acting through cAMP- and Ca2 -mediated activation of complex-mediated actin polymerization. Our previous studies have protein phosphatase 2A and 2B, respectively (4, 7). These results found WAVE1 to be inhibited by Cdk5-mediated phosphorylation indicate that WAVE1 is a neuronal activity-regulated phospho- in brain and to play a role in the regulation of dendritic spine mor- protein in the striatum. phology. Here we report that mice in which WAVE1 was knocked out We previously identified a pivotal role for Cdk5/p35 in cocaine- (KO) in neurons expressing the D1 dopamine receptor (D1-KO), but induced adaptive changes in brain (8). -
Brain & Behavior Research Foundation 30Th Anniversary Celebration
Brain & Behavior Research Foundation INTERNATIONAL30th Anniversary Celebration AWARDS DINNER FRIDAY, OCTOBER 27th The Pierre 2017 Celebrating our Pardes Humanitarian Prizewinners and Outstanding Achievement Prizewinners WELCOME Welcome to our 2017 International Awards Dinner and our celebration of the 30th anniversary of the Brain & Behavior Research Foundation. This year’s program honors our 2017 Outstanding Achieve- ment Prizewinners, the recipient of the Pardes Humanitarian Prize in Mental Health, and, includes a special Pardes Humanitarian Prize Honorary Tribute to the late Constance E. Lieber, whose leadership as President and President Emeritus of our Foundation, touched so many lives. Connie was one of the world’s greatest public advocates for mental health and psychiatric research and care and she continues to be our guiding light. This year’s Pardes Humanitarian Prize honors Doctors Without Borders/Médecins San Frontières (MSF) for their transformative work in providing mental health care as an integrated component of medical aid during natural and man-made emergencies and chronic crises. Founded in 1971, MSF provides aid in nearly 60 countries and received the 1999 Nobel Peace Prize for its independent, rapid, and fearless work during humanitarian catastrophes. Bestowed annually since 2014, the Pardes Prize recognizes a person(s) or organization whose human- itarian work is transformative and of great magnitude, changing the lives and bringing the joy of living to those facing challenges to mental health. The Prize focuses public attention on the burden of mental illness on individuals and on society, and the urgent need to expand and enhance mental health services both in the developed world and in developing countries. -
Localization of Dopamine D, Receptor Mrna and D, and D, Receptor Binding in the Rat Brain and Pituitary: an in Situ Hybridization-Receptor Autoradiographic Analysis
The Journal of Neuroscience, August 1990, 70(8): 2587-2800 Localization of Dopamine D, Receptor mRNA and D, and D, Receptor Binding in the Rat Brain and Pituitary: An in situ Hybridization-Receptor Autoradiographic Analysis Alfred Mansour,’ James H. Meador-Woodruff,i James R. Bunzow,2 Olivier Civelli,* Huda Akil,’ and Stanley J. Watson’ ‘Mental Health Research Institute, University of Michigan, Ann Arbor, Michigan 48109-0720, and *Vellum Institute for Advanced Biomedical Research, The Oregon Health Sciences University, Portland, Oregon 97201 Several lines of evidence suggest the existence of multiple Cumulative evidence suggeststhe existence of at least 2 distinct dopamine receptor subtypes, referred to as D, and D,. The dopaminergic receptor subtypes, referred to as D, and D,. D, present study examines the distribution of these dopamine dopamine (DA) receptors are positively coupled to adenylate binding sites in the rat brain and pituitary in relation to the cyclase (Stoof and Kebabian, 1984), widely distributed in the distribution of D, receptor mRNA using a combination of in CNS (Boyson et al., 1986; Dawson et al., 1986; Dubois et al., vitro receptor autoradiographic and in situ hybridization 1986; Bouthenet et al., 1987; Wamsley et al., 1989), and abun- techniques. 3H-Raclopride and 3H-SCH23390 (in the pres- dant in the parathyroid gland (Attie et al., 1980). D, DA recep- ence of 1 ELM ketanserin) were used to label D, and D, re- tors, on the other hand, are either not coupled to adenylate ceptor binding sites, respectively, while a 495 bp cRNA probe cyclase (Memo et al., 1986) or negatively coupled (Onali et al., synthesized from the Sac I-Bglllfragment of a rat D, receptor 1985) and are densely distributed in the basal ganglia (Martres cDNA was used to visualize the D, receptor mRNA. -
KAFUI DZIRASA, MD Phd
KAFUI DZIRASA, MD PhD 421 Bryan Research, Box 3209 E-mail: [email protected] 311 Research Drive Durham, North Carolina 27710 Duke University Medical Center Office: (919) 681-7371 EDUCATION: University of Maryland Baltimore County, Baltimore, MD June 1996-May 2001 Bachelor of Science in Chemical Engineering, Magna cum laude Meyerhoff Scholar Duke University Graduate School, Durham NC August 2003-March 2007 Doctor of Philosophy in Neurobiology Thesis: Electrophysiological Correlates of Neurological and Psychiatric Disease Advisor: Miguel Nicolelis Postdoctoral Research August 2007-March 2009 Duke University, Durham, NC Advisor: Miguel Nicolelis Duke University School of Medicine, Durham, NC August 2001-May 2009 Doctor of Medicine Medical Scientist Training Program Duke University Hospital, Durham, NC July 2010-June 2016 Residency, General Psychiatry North Carolina Medical License License #: 2016-02599 License Status: Active EMPLOYMENT HISTORY: K. Ranga Rama Krishnan Endowed Associate Professor, Tenure Track, Department of Psychiatry and Behavioral Sciences. Duke University Medical Center. May 2018-Current Associate Professor, Tenure Track, Department of Psychiatry and Behavioral Sciences. Duke University Medical Center. September 2017-Current Assistant Professor, Tenure Track, Department of Psychiatry and Behavioral Sciences. Duke University Medical Center. December 2013-August 2017 Assistant Research Professor, Department of Neurobiology. Duke University. October 2012-Current. Assistant Professor, Department of Biomedical Engineering. Duke University. March 2012-Current. Visiting Professor of Neuroscience, Edmond and Lily Safra International Institute of Neurosciences of Natal (ELS-IINN). August 2011-Current. General Psychiatry Resident, Department of Psychiatry and Behavioral Sciences. Duke University Medical Center. June 2010-June 2016. Assistant Professor, Research Non-Tenure Track, Department of Psychiatry and Behavioral Sciences. -
Regulation of Hypothalamic Magnocellular Neuropeptides and Their Mrnas in the Brattleboro Rat: Coordinate Responses to Further Osmotic Challenge
The Journal of Neuroscience, October 1988, 8(10): 3785-3796 Regulation of Hypothalamic Magnocellular Neuropeptides and their mRNAs in the Brattleboro Rat: Coordinate Responses to Further Osmotic Challenge Thomas G, Sherman,’ Robert Day,’ Olivier Civelli,2 James Douglass,* Edward Herbert,’ Huda Akil,l and Stanley J. Watson’ ‘Mental Health Research Institute, University of Michigan, Ann Arbor, Michigan 48109, arid Wsllum Institute for Advanced Biomedical Research, Oregon Health Sciences University, Portland, Oregon 97281 A paradigm was developed for the chronic osmotic stimu- feedback-regulated by AVP, most likely via plasma osmo- lation of homoeygous diabetes insipidus rats of the Brattle- larity, and that oxytocin neurons are modulated by peptides boro strain, a strain that fails to synthesize vasopressln. This derived from pro-dynorphin. study examines the adaptation of 2 sets of coexisting pep- tide hormone magnocellular neurons in the hypothalamo- The hypothalamo-neurohypophyscal system (HNS) is a neu- neurohypophyseal system (HNS) of Long Evans (LE), Brat- roendocrine pathway comprised of magnocellularneurons with- tleboro heterozygote (HZ), and Brattleboro homozygote (DI) in the hypothalamic paraventricular (PVN) and supraoptic(SON) rats: (1) the arginine+asopressin (AVP)/dynorphin (DYN) nuclei, which project to the posterior pituitary, where their se- neurons, and (2) the oxytocin (OT)/cholecystokinin (CCKI) cretory products have accessto the circulatory system. Mag- neurons of the paraventricular and supraoptic nuclei, which nocellular neurons of the HNS are classically known for the project to the posterior pituitary. The regimen of chronic synthesisof the blood-borne nonapeptide hormones arginine*- intermittent salt-loading (CISL) involved the replacement of vasopressin(AVP) and oxytocin (OT), 2 of the original peptide 2% saline for normal drinking water for 18 hr/d. -
Rhoda and Bernard Sarnat International Prize in Mental Health 2016 Honorees
Rhoda and Bernard Sarnat International Prize in Mental Health 2016 Honorees Steven Hyman, MD Director, Stanley Center for Psychiatric Research Broad Institute of Harvard and MIT Sir Robin Murray, MD Professor, Institute of Psychiatry King’s College London The National Academy of Medicine (NAM) awarded the 2016 Rhoda and Bernard Sarnat International Prize in Mental Health to Steven Hyman and Robin Mur- ray. Hyman was awarded the prize for his leadership in furthering understand- ing and treatment of psychiatric disorders as biological diseases. Murray was awarded the prize for integrating the biological, environmental, and social aspects of schizophrenia and thereby improving the lives of patients and their families. “Through their pioneering, innovative work, Dr. Hyman and Dr. Murray have each greatly advanced our understanding of mental health disorders and helped develop effective treatments that have changed patients’ lives for the better,” said NAM President Victor J. Dzau. Hyman has been a leader in the world of mental illness research and treatment for over three decades. As a physician and scientist in the 1980s and 1990s, Hy- man was at the forefront of the movement to understand the biological bases of mental disorders. Hyman led the National Institute of Mental Health from 1996 to 2001, when he made neuroscience and genetics central to the NIMH mission and launched several large-scale clinical trials to inform practice and treatment strategies, seeking to identify more effective real-world treatments for schizo- phrenia, bipolar disorder, and childhood and adolescent depression and other disorders. Following his tenure at NIH, Hyman assumed an instrumental role in the revisions of the Diagnostic and Statistical Manual of Mental Disorders (DSM- 5) and the World Health Organization’s International Classification of Diseases, encouraging dimensional approaches to mental illnesses that take into account genetics, co-morbidities, and emerging neuroscience data. -
50 Years of INRC: 1969 to 2019 – 55 Years of Our Rockefeller University Research and 50 to 60 Years of Opioid Research Mary Jeanne Kreek, M.D
50 Years of INRC: 1969 to 2019 – 55 Years of our Rockefeller University Research and 50 to 60 Years of Opioid Research Mary Jeanne Kreek, M.D. Patrick E. and Beatrice M. Haggerty Professor Head of Laboratory The Laboratory of the Biology of Addictive Diseases The Rockefeller University Senior Physician, The Rockefeller University Hospital International Narcotics Research Conference July 8, 2019 New York, NY Funded primarily by Dr. Miriam and Sheldon Adelson Medical Research Foundation, NIH-NIDA, NIH-NIAAA, NIH-CRR, Tri-Institutional Therapeutics Discovery Institute, Robertson Therapeutic Development Fund, and others International Narcotics Research Conference Founders Lecturers (First Awardee 1999) 1999 Eric J. Simon 2009 R. Alan North 2000 Brian M. Cox 2010 Masamichi Satoh 2001 Philip S. Portoghese 2011 Charles Chavkin 2002 Lars Terenius 2012 F. Ivy Carroll 2003 Bernard Roques 2013 Graeme Henderson 2004 Ji-Sheng Han 2014 Christopher Evans 2005 Mary Jeanne Kreek Brigitte Kieffer 2006 Huda Akil 2015 Gavril Pasternak (d. 2019) Stan Watson 2016 Lakshmi Devi 2007 Volker Hoellt 2017 John Traynor Horace Loh 2018 Macdonald Christie 2008 Jan van Ree 2019 Sol Snyder Kreek 2019 International Narcotics Research Conference Founders Lecturers at this 50th Anniversary Meeting 1999 Eric J. Simon 2009 R. Alan North 2000 Brian M. Cox 2010 Masamichi Satoh 2001 Philip S. Portoghese 2011 Charles Chavkin 2002 Lars Terenius 2012 F. Ivy Carroll 2003 Bernard Roques 2013 Graeme Henderson 2004 Ji-Sheng Han 2014 Christopher Evans 2005 Mary Jeanne Kreek Brigitte Kieffer 2006 Huda Akil 2015 Gavril Pasternak (d. 2019) Stan Watson 2016 Lakshmi Devi 2007 Volker Hoellt 2017 John Traynor Horace Loh 2018 Macdonald Christie 2008 Jan van Ree 2019 Sol Snyder Kreek 2019 Ji-Sheng Han cannot attend this 50th Anniversary meeting because of a family illness and sends his regards, along with this photo of him with his family. -
Dynorphin Immunocytochemistry in the Rat Central Nervous System
Peptides. Vol. 3. pp. 941-954, 1982. Printed in the U.S.A. Dynorphin Immunocytochemistry in the Rat Central Nervous System HENRY KHACHATURIAN, STANLEY J. WATSON, 1 MICHAEL E. LEWIS, DAVID COY,* AVRAM GOLDSTEIN,tAND HUDA AKIL Mental Health Research Institute, University of Michigan, Ann Arbor, MI 48109 *Department of Medicine, Tulane University School of Medicine, New Orleans, LA 70195 and tAddiction Research Foundation, Stanford University, Palo Alto, CA 94394 Received 16 August 1982 KHACHATURIAN, H., S. J. WATSON, M. E. LEWIS, D. COY, A. GOLDSTEIN AND H. AKIL. Dynorphin im- munocytochemisto, in the rat central nervous system. PEPTIDES 3(6) 941-954, 1982.--The distribution ofdynorphin in the central nervous system was investigated in rats pretreated with relatively high doses (3(10--400/zg) of colchicine administered intracerebroventricularly. To circumvent the problems of antibody cross-reactivity, antisera were generated against differ- ent portions as well as the full dynorphin molecule (i.e., residues 1-13, 7-17, or 1-17). For comparison, antisera to [Leu]enkephalin (residues 1-5) were also utilized. Dynorphin was found to be widely distributed throughout the neuraxis. lmmunoreactive neuronal perikarya exist in hypothalamic magnoceUular nuclei, periaqueductal gray, scattered reticular formation sites, and other brain stem nuclei, as well as in spinal cord. Additionally, dynorphin-positive fibers or terminals occur in the cerebral cortex, olfactory bulb, nucleus accumbens, caudate-putamen, globus pallidus, hypothalamus, sub- stantia nigra, periaqueductal gray, many brain stem sties, and the spinal cord. In many areas studied, dynorphin and enkephalin appeared to form parallel but probably separate anatomical systems. The results suggest that dynorphin occurs in neuronal systems that are immunocytochemically distinct from those containing other opioid peptides.