DOCSLIB.ORG

Diet-Induced Insulin Resistance Promotes Amyloidosis in a Transgenic Mouse Model of Alzheimer’S Disease1

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Diet-Induced Insulin Resistance Promotes Amyloidosis in a Transgenic Mouse Model of Alzheimer’S Disease1 Diet-induced insulin resistance promotes amyloidosis in a transgenic mouse model of Alzheimer’s disease1 LAP HO,*,2 WEIPING QIN,*,2 PATRICK N. POMPL,*,2 ZHONGMIN XIANG,* JUN WANG,* ZHONG ZHAO,* YUANZHEN PENG,* GINA CAMBARERI,* ANNE ROCHER,† CHARLES V. MOBBS,†,‡ PATRICK R. HOF,†,§ AND GIULIO MARIA PASINETTI*,3 *Neuroinflammation Research Laboratories, Department of Psychiatry and †Kastor Neurobiology of Aging Laboratories, Fishberg Research Center for Neurobiology, ‡Department of Geriatrics and Adult Development, and §Advanced Imaging Program, Mount Sinai School of Medicine, New York, New York, USA SPECIFIC AIMS CONCLUSIONS AND SIGNIFICANCE Insulin resistance, a proximal cause of Type II diabetes While AD accounts for most age-related dementia, AD (a non-insulin-dependent form of diabetes mellitus is clinically and neuropathologically similar to other (NIDDM)), is associated with an increased relative risk forms of dementia, e.g., vascular dementia (VaD). for Alzheimer’s disease (AD). To clarify how NIDDM Further complicating interpretation of dementia type, may influence Alzheimer’s disease (AD) neuropathol- a large body of recent evidence suggests that cardiovas- ogy, we explore the role of experimental NIDDM-like cular risk factors (CvRFs) (diet, life style factors, etc.) insulin resistance in the Tg2576 mouse model, which may promote pure AD-related neuropathology and AD develops AD type neuropathology. dementia even when VaD cases are excluded from the analysis. Thus, it may be that additional nonvascular pathogenic events are related to the increased risk of AD conferred by certain CvRFs (e.g., insulin resis- tance). Using the Tg2576 mouse model of AD-type PRINCIPAL FINDINGS neuropathology, we explored a potential cause-effect relationship between dietary conditions described pre- 1. We found that a diet that induces insulin resistance viously to promote NIDDM-like insulin resistance and ␤ ␤ ␤ promoted amyloidogenic -amyloid (A )A 1-40 and AD neuropathology. We report two major observations ␤ A 1-42 peptide generation (Fig. 1A) and amyloid plaque supporting the hypothesis that CvRFs such as insulin burden (Fig. 1B) in the brain of Tg2576 mice that resistance may directly promote the risk of AD-related corresponded with increased ␥-secretase activities and neuropathology. decreased insulin-degrading enzyme (IDE) activity. Our first observation is that diet-induced NIDDM-like Moreover, increased A␤ production coincided with insulin resistance results in the promotion of AD-type increased AD-type amyloid plaque burden in the brain amyloidosis in the brain coincidental to altered IR and impaired performance in a spatial water maze task signaling in the brain. We found that NIDDM-like (see online article). insulin resistance in Tg2576 mice significantly attenu- 2. Further exploration of the apparent interrelation- ated IR signaling in the brain as assessed by reduced ship of insulin resistance to brain amyloidosis revealed levels of Y1162/1163-IR␤ phosphorylation whereas the a functional decrease in insulin receptor (IR)-mediated total content of IR␤ remained unchanged. This evi- signal transduction in the brain, as suggested by de- dence is of high interest in that it supports the hypoth- creased IR ␤-subunit (IR␤)Y1162/1163 autophosphoryla- esis that NIDDM-like insulin resistance in Tg2576 mice tion and reduced phosphatidylinositol 3 (PI3)-kinase/ might influence signal transduction mechanisms down- pS473-AKT/Protein kinase (PK)-B in these same brain stream of the IR, which are known to promote amyloi- regions. dogenic A␤ peptide generation as shown for GSK-3. 3. In view of the inhibitory role of AKT/ PKB on Moreover, we found that increased activation of glycogen synthase kinase (GSK)-3␣ activity that has GSK-3␣ and GSK-3␤ (as reflected by decreased pS21- been implicated in mechanisms associated with promo- GSK-3␣ and pS9-GSK-3␤) strongly correlated with in- tion of A␤ peptide generation, we explored the poten- creased ␥-secretase activity in the brain of insulin- tial inter-relationship between GSK-3 and ␥-secretase 21 ␣ activity. We found that decreased pS -GSK-3 and 1 pS9-GSK-3␤ phosphorylation (indicative of GSK-3␣/␤ To read the full text of this article, go to http://www.fasebj. ␥ org/cgi/doi/10.1096/fj.03-0978fje; doi: 10.1096/fj.03-0978fje activation) positively correlated with -secretase activity 2 These authors contributed equally to this work. in the brain of insulin-resistant relative vs. normoglyce- 3 Correspondence: One Gustave L. Levy Pl., Box 1230, New mic Tg2576 mice (Fig. 2A–C). York, NY 10029, USA. E-mail: [email protected] 902 0892-6638/04/0018-0902 © FASEB linemia, glucose intolerance, and increased body weight) can promote AD-type amyloidosis in the brain independent of altered cholesterol metabolism. This important given earlier evidence indicating that expo- sure of Tg2576 mice to a diet rich in cholesterol, can result in elevated cholesterol content in brain (and Figure 1. Diet-induced insulin resistance-mediated promotion of AD-type amyloid burden is associated with decreased IR signaling in the brain of Tg2576 mice. In this study nine- month-old insulin-resistant and normoglycemic Tg2576 fe- male mice were assessed for indexes of AD-type amyloid ␤ ␤ burden. A) ELISA detection of A 1Ϫ40 and A 1Ϫ42 peptide content and 22C11 immunopositive holo-amyloid precursor protein (APP) content in the hippocampal formation. B) Stereological cerebral cortical (neocortex and hippocampal formation) 6E10 immunopositive amyloid plaque volume and burden (amyloid plaque volume as a % of cerebral cortex volume). A, B) values represent means Ϯ se, n ϭ 5or6per group; *P Ͻ 0.05, **P Ͻ 0.01, ***P Ͻ 0.001 vs. control group (2-tailed Student’s t test). resistant Tg2576 mice. This evidence suggests that in Tg2576 mice, dietary conditions leading to NIDDM-like insulin resistance may result in altered IR signaling in the brain and eventually “unleash” GSK-3␣ (and GSK- 3␤) activity implicated in the promotion of ␥-secretase activity and the generation of amyloidogenic A␤ pep- tides. Our second observation was a significant decrease of IDE expression and activity in the brain of insulin- resistant Tg2576 mice, suggesting that NIDDM-like insulin resistance may have contributed to amyloidosis by interfering with IDE-mediated degradation of amy- loidogenic A␤ peptides. A role for IDE in A␤ degrada- ␥ tion was demonstrated by recent studies showing that Figure 2. Insulin resistance promotes -secretase activity in the brain of Tg2576 mice. A) Increased ␥-secretase activity in mice deficient for IDE exhibit increased cerebral accu- ␥ ␤ cerebral cortex (left panel) assessed by generation of -C- mulation of endogenous A peptides, as well as hyper- terminal fragment (CTF) from membrane associated APP insulinemia and glucose intolerance, both hallmarks of (normalized to holo-APP in the membrane preparation). NIDDM. Therefore, it would not be unexpected that Parallel Western blot analysis of holo-APP from total brain hyperinsulinemia in response to NIDDM (as we found extract (right panel) confirmed that the diet-induced insulin out in a diet-induced NIDDM mouse model) could resistance did not influence holo-APP expression. Inset: Rep- further impede A␤ degradation via competition with resentative cleavage products generated from membrane- bound APP; as expected, negative controls (no incubation) insulin for degradation by IDE. yielded no CTF-␥ cleavage product. B, C) Scatter plot analysis Our study presents the first experimental evidence to of ␥-secretase activity as a function of pS21-GSK-3␣/GSK-3␣ suggest that dietary treatment leading to a condition (B) and pS9-GSK-3␤/GSK-3␤ (C). Straight line represents that recapitulates NIDDM in humans (e.g., hyperinsu- best linear regression fit.. INSULIN RESISTANCE PROMOTES ALZHEIMER’S DISEASE 903 tive to strain/age/gender-matched WT control mice as assessed by a glucose tolerance test. This finding sug- gests that the content of amyloidogenic A␤ peptides in the brain of normoglycemic Tg2576 mice does not predicate conditions of altered glucose metabolism and that it is likely that the physiologic conditions resultant to NIDDM-like insulin resistance were responsible for the observed promotion of amyloidosis in Tg 2576 mice in this study. However, we note that previous evidence has indicated that Tg2576 mice have impaired plasma glucocorticoid and glucose regulation in response to restraint stress. While it is well established that CvRFs are significant and potent risks factor for AD, our study for the first time provides evidence supporting a potential direct Figure 3. Diet-induced insulin resistance may promote AD- role of diet induced NIDDM-like insulin resistance type amyloidosis via mechanisms involving ␥-secretase and conditions on AD neuropathology via the promotion of insulin-degrading enzyme (IDE). amyloidogenesis. Our studies strongly suggest that one mechanism by which diet-induced insulin resistance in serum) and a subsequent promotion of brain amyloid Tg2576 mice can significantly promote AD-type amy- deposition. For this reason we designed the present loidosis in the brain is through impairment of IR study to preclude this potential confound by using diets signaling resulting in elevation of ␥-secretase activities. containing ϳ100 fold less cholesterol than that of Our studies also suggest that NIDDM may further previous cholesterol-based studies. Moreover, in con- contribute to amyloidosis by attenuating A␤ degrada- trol studies, we confirmed that diet-induced NIDDM- tion by mechanisms
Load more

Recommended publications
  • Missing Link Connects Diabetes and Alzheimer's Disease
    Missing Link Connects Diabetes and Alzheimer’s Disease A gene called PGC-1! is associated with the onset of Type 2 diabetes, associated with dementia and but it has shown to decrease in Alzheimer’s disease dementia cases. an accumulation in the brain of The gene is a potential target for regulating glucose, according to an abnormal protein known as new research led by Giulio Maria Pasinetti, MD, PhD, the Aidekman "-amyloid. This abnormal protein Family Professor in Neurology, and Professor of Psychiatry and causes plaque buildup in the Geriatrics and Adult Development. The study was recently published brain, which is linked to cognitive in Archives of Neurology. deterioration in Alzheimer’s disease. The PGC-1! gene, which plays an important role in regulating We may be able to link a gene—whose glucose metabolism, is considered a potential target for treating alteration may lead to diabetes—to a Type 2 diabetes. Giulio Maria Pasinetti, MD, PhD mechanism that would promote conditions Using a mouse model of associated with Alzheimer’s disease. Alzheimer’s disease, Dr. Pasinetti and his team also found that promoting PGC-1! content in brain cells reduces the hyperglycemic- — GIULIO MARIA PASINETTI, MD, PHD mediated production of "-amyloid. The findings could help researchers identify potential pharmacological treatments that might promote PGC-1! expression Previous studies suggest that Type 2 diabetes is a risk factor for in the brain cells of Alzheimer’s patients. “We need to discover Alzheimer’s disease. The relationship between the two conditions is new therapeutic approaches for Alzheimer’s disease by looking at “a fascinating new area of research,” says Dr.
    [Show full text]
  • Cytokine Gene Expression As a Function of the Clinical Progression of Alzheimer Disease Dementia
    ORIGINAL CONTRIBUTION Cytokine Gene Expression as a Function of the Clinical Progression of Alzheimer Disease Dementia James D. Luterman, PhD; Vahram Haroutunian, PhD; Shrishailam Yemul, PhD; Lap Ho, PhD; Dushyant Purohit, MD; Paul S. Aisen, MD; Richard Mohs, MD; Giulio Maria Pasinetti, MD, PhD Background: Inflammatory cytokines have been linked gyrus (P,.01). When stratified by the Consortium to to Alzheimer disease (AD) neurodegeneration, but little Establish a Registry for Alzheimer’s Disease (CERAD) is known about the temporal control of their expression neuropathological criteria, IL-6 mRNA expression in in relationship to clinical measurements of AD demen- both the entorhinal cortex (P,.05) and superior tem- tia progression. poral gyrus (P,.01) correlated with the level of neuro- fibrillary tangles but not neuritic plaques. However, in Design and Main Outcome Measures: We mea- the entorhinal cortex, TGF-b1 mRNA did not correlate sured inflammatory cytokine messenger RNA (mRNA) with the level of either neurofibrillary tangles or neu- expression in postmortem brain specimens of elderly sub- ritic plaques. Interestingly, in the superior temporal jects at different clinical stages of dementia and neuro- gyrus, TGF-b1 mRNA expression negatively correlated pathological dysfunction. with neurofibrillary tangles (P,.01) and showed no relationship to the pathological features of neuritic Setting and Patients: Postmortem study of nursing plaques. home patients. Conclusions: The data are consistent with the hypoth- Results: In brains of cognitively normal control sub- esis that cytokine expression may differentially contrib- jects, higher interleukin 6 (IL-6) and transforming ute to the vulnerability of independent cortical regions growth factor b1 (TGF-b1) mRNA expression was during the clinical progression of AD and suggest that observed in the entorhinal cortex and superior temporal an inflammatory cytokine response to the pathological gyrus compared with the occipital cortex.
    [Show full text]
  • View Final Program
    142nd ANNUAL MEETING OF THE AMERICAN ANA2017 NEUROLOGICAL ASSOCIATION SAN DIEGO, CA • OCTOBER 15-17, 2017 SHERATON SAN DIEGO HOTEL & MARINA EXPLORE • EXAMINE • INVESTIGATE FINAL PROGRAM OCTOBER 14, 2017 | Pre-Meeting Symposium: Big Science and the BRAIN Initiative 2017.MYANA.org 142nd ANNUAL MEETING OF THE AMERICAN ANA2017 NEUROLOGICAL ASSOCIATION SAN DIEGO, CA • OCTOBER 15 -17, 2017 SHERATON SAN DIEGO HOTEL & MARINA ND Please note some session titles may have changed since this program was printed. Please refer THE 142 ANA to your Mobile app for the most current session updates. ANNUAL MEETING LETTER FROM THE CHAIR 3 Enjoy outstanding scientific SCHEDULE AT A GLANCE 4 symposia covering the latest HOTEL FLOOR PLANS 6 research in the fields of neurology and neuroscience GENERAL INFORMATION 7 while taking the opportunity WIRELESS CONNECTION 8 to network with leaders in the world of academic neurology CONTINUING MEDICAL EDUCATION 8 at the 142nd ANA Annual ANNUAL MEETING MOBILE APP 8 Meeting in San Diego, CA, October 15-17, 2017. PROGRAMS BY DAY 9 SATURDAY OCT 14 9 MEETING LOCATION SUNDAY OCT 15 9 Sheraton San Diego MONDAY OCT 16 17 Hotel & Marina 1380 Harbor Island Drive TUESDAY OCT 17 25 San Diego, California 92101 IN MEMORIAM 28 ONSITE MEETING CONTACTS SPEAKER ABSTRACTS 29 Registration and meeting questions: THANK YOU TO OUR SUPPORTERS & EXHIBITORS 42 [email protected] FUTURE MEETING DATES 42 OR visit the registration desk Bay View Foyer 2017 AWARDEES 43 (located in Marina Tower Lobby Level) ACADEMIC NEUROLOGY REPRESENTATIVES FROM JAPAN 47 Saturday, October 14 2017 ABSTRACT REVIEWERS 48 3:00 PM–7:00 PM BOARD OF DIRECTORS 49 Sunday, October 15 6:00 AM–5:45 PM ANA 2017 COMMITTEES, SUBCOMMITTEES & TASK FORCES 50 Monday, October 16 6:30 AM–5:45 PM Tuesday, October 17 6:30 AM–2:15 PM #ANAMTG2017 ANA 2017 FROM THE CHAIR Dear Colleagues, It is a pleasure to welcome you to the 142nd Annual Meeting of the American Neurological Association (ANA).
    [Show full text]
  • Obesity & Weight Management
    Giulio Maria Pasinetti, J Obes Wt Loss Ther 2012, 2:9 http://dx.doi.org/10.4172/2165-7904.S1.003 International Conference and Exhibition on Obesity & Weight Management December 3-5, 2012 DoubleTree by Hilton Philadelphia, USA HDAC IIa-specific inhibitors as a potential novel therapy for type 2 diabetes-mediated cognitive deterioration in alzheimer’s disease Giulio Maria Pasinetti Mount Sinai School of Medicine, USA ur laboratory recently demonstrated that epigenetic chromatin modifications associated with type-2 diabetes (T2DM) may Oplay a role in brain pathophysiology in neurodegenerative disorders. We previously discovered that there are significant changes in the expression of select chromatin modification enzymes, such as histone deacetylases (HDACs), in the brains of T2DM subjects compared to control subjects, and that these changes coincide with altered expression of proteins involved in synaptic function, such as PSD95 and synaptophysin. We hypothesized that T2DM may induce epigenetic modifications associated with increased susceptibility to Alzheimer’s disease (AD)-type neurodegeneration. Using a mouse model of diet- induced T2DM, we found that, similar to humans, T2DM mice showed differential expression of epigenetic-modifying enzymes in the brain compared to controls. In particular, we found significant up-regulation of HDAC class IIa, including HDACs 4, 5, and 9, in the brains of diabetic mice. These alterations coincided with increased susceptibility to oligomeric Aβ (oAβ) induced synaptic toxicity and oAβ-induced synaptic dysfunction, as assessed by long term potentiation (LTP). Most interestingly, we found that inhibition of class IIa HDACs using an HDAC IIa-specific inhibitor, MC1568, increased transcription levels of PSD95 and synaptophysin in primary neuron cultures from C57Bl6/J mice and prevented LTP deficits found in old-T2DM mouse ex vivo hippocampal slices.
    [Show full text]
  • NIH Public Access Author Manuscript J Neurochem
    NIH Public Access Author Manuscript J Neurochem. Author manuscript; available in PMC 2009 August 1. NIH-PA Author ManuscriptPublished NIH-PA Author Manuscript in final edited NIH-PA Author Manuscript form as: J Neurochem. 2008 August ; 106(4): 1503±1514. doi:10.1111/j.1471-4159.2008.05454.x. METABOLIC SYNDROME AND THE ROLE OF DIETARY LIFESTYLES IN ALZHEIMER’S DISEASE Giulio Maria Pasinetti1 and Jacqueline A. Eberstein2 1Center of Excellence for Research in Complementary and Alternative Medicine in Alzheimer©s Disease, Department of Psychiatry, The Mount Sinai School of Medicine 2Controlled Carbohydrate Nutrition, LLC. Abstract Since Alzheimer’s disease (AD) has no cure or preventive treatment, an urgent need exists to find a means of preventing, delaying the onset, or reversing the course of the disease. Clinical and epidemiological evidence suggests that lifestyle factors, especially nutrition, may be crucial in controlling AD. Unhealthy lifestyle choices lead to an increasing incidence of obesity, dyslipidemia and hypertension — components of the metabolic syndrome. These disorders can also be linked to AD. Recent research supports the hypothesis that calorie intake, among other nongenetic factors, can influence the risk of clinical dementia. In animal studies, high calorie intake in the form of saturated fat promoted AD-type amyloidosis, while calorie restriction via reduced carbohydrate intake prevented it. Pending further study, it is prudent to recommend to those at risk for AD — e.g., with a family history or features of metabolic syndrome, such as obesity, insulin insensitivity, etc. — to avoid foods and beverages with added sugars; to eat whole, unrefined foods with natural fats, especially fish, nuts and seeds, olives and olive oil; and to minimize foods that disrupt insulin and blood sugar balance.
    [Show full text]
  • The Innate Immune System and Inflammatory Priming: Potential Mechanistic Factors in Mood Disorders and Gulf War Illness
    REVIEW published: 23 July 2020 doi: 10.3389/fpsyt.2020.00704 The Innate Immune System and Inflammatory Priming: Potential Mechanistic Factors in Mood Disorders and Gulf War Illness Kyle J. Trageser 1, Maria Sebastian-Valverde 1, Sean X Naughton 1 and Giulio Maria Pasinetti 1,2* 1 Department of Neurology, Mount Sinai School of Medicine, New York, NY, United States, 2 Geriatric Research, Education and Clinical Center, James J. Peters Veterans Affairs Medical Center, Bronx, NY, United States Edited by: Gabriella Martino, University of Messina, Italy Gulf War Illness is a chronic multisystem disorder affecting approximately a third of the Reviewed by: Veterans of the Gulf War, manifesting with physical and mental health symptoms such as Lisa James, cognitive impairment, neurological abnormalities, and dysregulation of mood. Among the University of Minnesota Twin Cities, United States leading theories into the etiology of this multisystem disorder is environmental exposure to Kimberly A. Kelly, the various neurotoxins encountered in the Gulf Theatre, including organophosphates, National Institute for Occupational fi Safety and Health (NIOSH), nerve agents, pyridostigmine bromide, smoke from oil well res, and depleted uranium. United States The relationship of toxin exposure and the pathogenesis of Gulf War Illness converges on *Correspondence: the innate immune system: a nonspecific form of immunity ubiquitous in nature that acts to Giulio Maria Pasinetti respond to both exogenous and endogenous insults. Activation of the innate immune [email protected] system results in inflammation mediated by the release of cytokines. Cytokine mediated Specialty section: neuroinflammation has been demonstrated in a number of psychiatric conditions and may This article was submitted to help explain the larger than expected population of Gulf War Veterans afflicted with a Psychopathology, a section of the journal mood disorder.
    [Show full text]
  • Neuroscience Retreat 2012 Pamphlet
    THE 2012 Friedman Brain Institute and the NEUROSCIENCE TRAINING AREA photo by David Carpenter FOURTH ANNUAL NEUROSCIENCE RETREAT NEW YORK ACADEMY OF MEDICINE 1216 Fifth Avenue Friedman Brain Institute Leadership Team Director: Eric Nestler, MD, PhD, Department of Neuroscience Chairs Joshua Bederson, MD, Department of Neurosurgery Wayne Goodman, MD, Department of Psychiatry John Morrison, PhD, Dean, Graduate School of Biological Sciences Kristjan Ragnarsson, MD, Department of Rehabilitation Medicine Stuart Sealfon, MD, Department of Neurology Centers of Excellence Joseph Buxbaum, MSc PhD Chief, Center of Excellence on Neurodevelopment Disorders Patrizia Casaccia, MD, PhD Chief, Center of Excellence on Myelin Disorders: Mechanisms & Repair Samuel Gandy, MD, PhD Chief, Center of Excellence on Neurodegeneration Patrick Hof, MD Chief, Center of Excellence on Brain Aging Yasmin Hurd, PhD Chief, Center of Excellence on Mood & Motivation Ehud Kaplan, PhD Chief, Center of Excellence on Computational & Systems Neuroscience Giulio Maria Pasinetti, MD, PhD Chief, Center of Excellence on Novel Neurodiagnostics & Neurotherapeutics Matthew Shapiro, PhD Chief, Center of Excellence on Cognition & Neural Plasticity 4th Annual Neuroscience Retreat Committee Retreat Organizers: Zhenyu Yue, PhD (Neurology) and Matthew Shapiro, PhD (Neuroscience) Retreat Administrators: Marie Kopp, Celeste Reyes, Jenny Rivera, and Veronica Szarejko Page 2 FRIEDMAN BRAIN INSTITUTE 4th Annual Neuroscience Retreat NEW YORK ACADEMY OF MEDICINE 1216 Fifth Avenue (corner of 103rd
    [Show full text]
  • Theme: Nano-Bio-Electronics
    10th Annual World Congress of SBMT on Brain, Spinal Cord Mapping and Image Guided Therapy May 12, 13, 14, 2013 Society for Brain Mapping and Therapeutics - SBMT Breaking BoundariesAnnual of Science, Technology, world Medicine, Congress Art and Healthcare Policyof th SBMT on Brain, 10 Cord Mapping and Breaking Boundaries of Science, Technology, Society for Brain Mapping and Therapeutics - SBMT Medicine, Art and Healthcare Policy THEME: NANO-BIO-ELECTRONICS Baltimore Convention Center, May 12, 13, Baltimore, Maryland 14, 2013 United States of America www.worldbrainmapping.org 1 th Annual world Congress 10 of SBMT on Brain, Cord Mapping and Breaking Boundaries of Science, Technology, Medicine, Art and Healthcare Policy INFO Society for Brain Mapping and Therapeutics - SBMT SBMT Global Headquarters 8159 Santa Monica Blvd., Suite 200 West Hollywood, CA 90046 ontents C Tel: 310.500.6196 Fax: 323.654.3511 [email protected] SBMT (Mission statement, Educational objectives, Annual world congress, Congress chairs, Charter.)...............p. 3-4 WorldBrainMapping.org Continuing Medical Education need assessment ...................p.5 CME ACCREDITATION Continuing Medical Education disclosures.................p.6-8 Society Board of Directors.............p.10-11 Scientific Committee............p.12-15 Accreditation/designation Statement: SBMT Letter from the Founder............p.16-17 (Babak Kateb) This activity has been planned and implemented in accor‐ SBMT President address..................p.18 dance with the Essential Ar‐ (Kuldip Sidhu) eas and policies of the Ac‐ creditation Council for Con‐ SBMT Program …....... p.19-21 tinuing Medical Education Keynote speakers .......... p.22-26 through the joint sponsorship of the International Society Timetable ............p.27-29 for Magnetic Resonace in Sunday May 12 - Scientific program ...........p.30-36 Medicine (ISMRM) and the Society for Brain Mapping & Monday May 13 - Scientific program .........
    [Show full text]
  • First Annual Symposium Center for Molecular Integrative Neuroresilience
    First Annual Symposium Center for Molecular Integrative Neuroresilience Icahn School of Medicine at Mount Sinai Program Director Giulio Maria Pasinetti http://icahn.mssm.edu/research/molecular-neuroresilience June 15th, 2016 from 9:00am – 5:00pm New York Academy of Medicine, 1216 5th Ave, New York, NY 10029 Topics will include: • Stress-induced psychological and • Characterization of natural compounds cognitive impairment for therapeutic and preventive • Mechanisms of neuroresilience and interventions proteostasis • Role of the microbiome in promoting therapeutic efficacy No registration costs • Free breakfast and lunch RSVP to [email protected] by June 8th TABLE OF CONTENTS Agenda of the Symposium…………………………………………………………………………………..2 Mission Statement/Collaborating Institutions/Acknowledgements of the Center…….………..…4 Overview of Research Projects and Cores…………………………….…………….………….………..5 External Advisory Committee Members…...…………………….…………….……………………...…20 Center Investigators….……………………………………………….…………….………….…………...21 Biographies of Project and Core Leaders…………………….…………….……………………...……23 Progress Report of Center Activities – Year 1…………………………….…………….……..……….27 Scientific Abstracts from the Poster Session of the Symposium………….……………………….53 1 AGENDA OF SYMPOSIUM Wednesday, June 15th, 2016 9:00am – 9:30am Registration and breakfast 9:30am – 9:45am Introduction and overview of the Center Giulio Maria Pasinetti, MD, PhD Saunders Family Chair and Professor of Neurology 9:45am – 10:15am Polyphenol compounds promote resilience to social stress (Project
    [Show full text]
  • In the News February 5, 2018
    From: ITNDaily Subject: Mount Sinai In The News - February 5, 2018 Date: Monday, February 05, 2018 3:03:34 PM Attachments: ATT00001.txt In the News February 5, 2018 Genetic Engineering & Biotechnology News – February 5 Grape-Derived Compounds May Help To Prevent Depression Scientists have identified two grape-derived compounds that can effectively help to treat and protect against stress-induced depression in mice, and which could represent promising new candidates for treating depression in humans. The compounds, dihydrocaffeic acid (DHCA) and malvidin-3'-O- glucoside (Mal-gluc), trigger epigenetic changes in genes that affect inflammation and synaptic plasticity, mechanisms that aren’t addressed by current antidepressants. “Our approach to use a combination treatment of DHCA and Mal-gluc to simultaneously inhibit peripheral inflammation and modulate synaptic plasticity in the brain works synergistically to optimize resilience against chronic stress-induced depression-like phenotypes,” said lead researcher, Giulio Maria Pasinetti, PhD, MD, Saunders professor of neurology and program director of the Center for Molecular Integrative Neuroresilience at the Icahn School of Medicine at Mount Sinai. “The discovery of these new, natural grape-derived polyphenol compounds targeting cellular and molecular pathways associated with inflammation may provide an effective way to treat a subset of people with depression and anxiety, a condition that affects so many people." - Giulio Maria Pasinetti, PhD, MD, Saunders Professor, Neurology, Program Director,
    [Show full text]
  • Program at Glance
    RDS-Summit Inaugural Reward Deficiency Syndrome Summit Reward Deficiency Syndrome (RDS) in the 21st Century: Epigenetics, Neurogenetic, Neuroimaging Tools for Therapy and Recovery Sponsors November 16-18, 2015 San Francisco, USA Program at Glance November 16, 2015 @ SIERRA B 08:30-09:00 Registrations 09:00-09:30 Introduction to the Reward Deficiency Syndrome Summit 09:30-12:20 Keynote Session I 12:20-17:00 Scientific Session I 17:00-18:00 Special Evening Movie I November 17, 2015 @ SIERRA B 09:00-10:40 Keynote Session II 11:00-15:40 Scientific Session II 16:00-17:00 Special Evening Movie II November 18, 2015 @ SIERRA B 09:30-11:30 Scientific Session III DAY 1 Monday, November 16, 2015 Keynote Session I @ SIERRA B Keynote Session I : 09:30-12:20 09:30-09:55 09:55-10:20 Kenneth Blum David E. Smith University of Florida, USA University of California at San Francisco, USA Presentation on: “Dopamine Resistance” in Brain Presentation on: Process Addictions and Addiction Reward Circuitry as a Function of Genetic Addiction Transfer Risk Score (Garspdx) Polymorphisms in RDS: Synaptamine Complex Variant (Kb220z) Induced “Dopamine Sensitivity” as a Pro-recovery Agent David E. Smith is recognized as a national leader in the treatment of addictive disease, the psychopharmacology of drugs, new research Kenneth Blum is widely designated as Father strategies in the management of drug abuse of Psychiatric Genetics because of the DRD2 problems, and appropriate prescribing practices gene and its correlation with various psychiatric for physicians. He teaches that addiction is a disorders including the “Reward Deficiency primary medical illness which is best treated in Syndrome (RDS)” which term he has coined.
    [Show full text]
  • Self-Disgust Is Associated with Loneliness, Mental Health Difficulties and Eye-Gaze Avoidance in War Veterans with PTSD
    This is a repository copy of Self-disgust is associated with loneliness, mental health difficulties and eye-gaze avoidance in war veterans with PTSD. White Rose Research Online URL for this paper: http://eprints.whiterose.ac.uk/166460/ Version: Published Version Article: Ypsilanti, A., Gettings, R., Lazuras, L. et al. (3 more authors) (2020) Self-disgust is associated with loneliness, mental health difficulties and eye-gaze avoidance in war veterans with PTSD. Frontiers in Psychology, 11. 559883. ISSN 1664-1078 https://doi.org/10.3389/fpsyg.2020.559883 Reuse This article is distributed under the terms of the Creative Commons Attribution (CC BY) licence. This licence allows you to distribute, remix, tweak, and build upon the work, even commercially, as long as you credit the authors for the original work. More information and the full terms of the licence here: https://creativecommons.org/licenses/ Takedown If you consider content in White Rose Research Online to be in breach of UK law, please notify us by emailing [email protected] including the URL of the record and the reason for the withdrawal request. [email protected] https://eprints.whiterose.ac.uk/ ORIGINAL RESEARCH published: 30 October 2020 doi: 10.3389/fpsyg.2020.559883 Self-Disgust Is Associated With Loneliness, Mental Health Difficulties, and Eye-Gaze Avoidance in War Veterans With PTSD Antonia Ypsilanti1*, Richard Gettings1, Lambros Lazuras1, Anna Robson1, Philip A. Powell2 and Paul G. Overton3 1 Department of Psychology, Sociology and Politics, Sheffield Hallam University, Sheffield, United Kingdom, 2 School of Health and Related Research (ScHARR), The University of Sheffield, Sheffield, United Kingdom, 3 Department of Psychology, The University of Sheffield, Sheffield, United Kingdom In the present study, we examined, for the first time, the association between self- Edited by: Giulio Maria Pasinetti, disgust, loneliness, and mental health difficulties in war veterans diagnosed with PTSD.
    [Show full text]