DOCSLIB.ORG

Cytokine Gene Expression As a Function of the Clinical Progression of Alzheimer Disease Dementia

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read 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. Compared effects of AD does not occur until the late stages of the with age-matched controls, subjects with severe/ disease. These findings have implications for the design terminal dementia, but not subjects at earlier disease of anti-inflammatory treatment strategies. stages, had higher IL-6 and TGF-b1 mRNA expression in the entorhinal cortex (P,.01) and superior temporal Arch Neurol. 2000;57:1153-1160 EVERAL CYTOKINES have been (mRNA) level is increased in postmor- associated with Alzheimer tem AD brains10 and correlates with amy- disease (AD) neuropathol- loid deposition in cerebral blood vessels. ogy. The level of the proin- However, TGF-b1 may also have nonin- flammatory cytokine inter- flammatory functions and may play an im- From the Neuroinflammation leukin 6 (IL-6) is increased in the brain, portant role in the growth and survival of S 11-13 Research Laboratories, blood, and cerebrospinal fluid of patients neurons in the AD brain. The expres- 1-6 Department of Psychiatry with AD, and IL-6 has been implicated sion of the cytokine tumor necrosis fac- (Drs Luterman, Yemul, Ho, in the transformation of diffuse to neu- tor a (TNF-a) is decreased in the frontal and Pasinetti), Department of ritic plaques in the AD brain.7 Interleu- cortex, superior temporal gyrus, and en- Pathology (Dr Purohit), and kin 1 (IL-1) has also been linked to amy- torhinal cortex of AD patients compared Psychiatry (Dr Mohs), Mount loid plaque transition from the diffuse to with non-AD controls14 and has both pro- Sinai School of Medicine, New dense core stage8 and the propagation of tective and destructive functions.15 York, NY; Department of the inflammatory signal through the in- Although cytokine expression has been Psychiatry, Bronx Veterans duction of S100b.4,9 Transforming growth shown to be regulated in the AD brain, pre- Affairs Medical Center, Bronx, NY (Dr Haroutunain); and factor b1 (TGF-b1) has been shown to vious studies evaluated postmortem tissue Department of Neurology, promote b-amyloid deposition in trans- from severely affected patients at the end 10 Georgetown University School genic mouse models and therefore may stages of AD. There is presently little infor- of Medicine, Washington, DC exacerbate amyloidogenic pathology. In mation on the dynamic expression of in- (Dr Aisen). addition, the TGF-b1 messenger RNA flammatory cytokines relative to the clini- (REPRINTED) ARCH NEUROL / VOL 57, AUG 2000 WWW.ARCHNEUROL.COM 1153 ©2000 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 METHODS complementary DNA (cDNA) templates for the following human cytokine genes was used: IL-6, TGF-b1, IL-1b, PATIENT SELECTION CRITERIA TNF-b, TNF-a, IL-1a, IL-1 receptor antagonist (IL-1Ra), and interferon gamma (IFN-g). The probe set also in- Human postmortem brains from AD and age-matched cluded the housekeeping genes L32 and glyceralde- non-AD cases were obtained from the Alzheimer’s Disease hyde-39 phosphate dehydrogenase (GAPDH) for normal- Research Center (ADRC) of the Mount Sinai School of Medi- ization of assay conditions. Details on the generation of cine, New York, NY. The cases selected had either no sig- phosphate P 32–labeled antisense RNA probes and condi- nificant neuropathological features or only neuropatho- tions of the RNase protection assay (RPA) are provided by logical features associated with AD.17,18 A multistep approach the manufacturer. The quantity of radioactively labeled based on cognitive and functional status during the last 6 RNase protection fragments was determined using a Mo- months of life was applied to the assignment of Clinical De- lecular Dynamics Storm 860 Phosphor Screen Scanner with mentia Rating (CDR) scores, as previously reported.17,18 Sub- the ImageQuant software package (Molecular Dynamics, jects were divided into groups on the basis of their CDR Sunnyvale, Calif). Each RPA analysis was conducted with scores as follows: 0, nondemented; 0.5, questionable de- 10 µg of total RNA, according to A260 values. Data are ex- mentia; 1, mild dementia; 2, moderate dementia; and 4 to pressed as a ratio of the specific mRNA of interest normal- 5, very severe dementia. ized to the constitutively expressed GAPDH mRNA. Nor- The extent of neurofibrillary tangle and b-amyloid neu- malization of cytokine mRNA signals to L32 mRNA did not ritic plaque deposition was assessed in accord with the Con- change the outcome results (not shown). sortium to Establish a Registry for Alzheimer’s Disease (CERAD) neuropathological battery.17-19 Multiple (5 in gen- RNA SAMPLE QUALITY AND EXCLUSION eral) high-power fields (3200, 0.5 mm2) were examined CRITERIA FOR RPA in each histological slide, containing specimens obtained from multiple brain regions, according to the CERAD re- Initial quality control consisted of agarose gel assessment of gional sampling scheme. The density of neurofibrillary ethidium bromide staining of both 18–Svedberg flotation unit tangles and neuritic plaques was rated on a 4-point scale (Sf) and 28-Sf ribosomal RNA (rRNA) integrity as well as as follows: 0, absent; 1, sparse; 3, moderate; and 5, severe. detection of low-molecular-weight “smearing” of degraded Plaques were visualized following either Bielschowsky sil- mRNA. All samples were subjected to RPA, regardless of ini- ver or thioflavine S staining.20,21 The investigators were blind tial quality control assessment. Only samples with nonde- to the clinical diagnosis of each case until all quantitative graded RNA determined by both ethidium bromide and RPA analyses were completed and values were assigned to each analysis were included in the study. For the entorhinal cor- specimen. tex, 19 (24%) of the 78 subjects were removed from the study because of poor RNA quality; for the superior temporal gy- RNA PREPARATION rus, 16 (20%) of 79 patients were removed; and for the oc- cipital cortex, 9 (36%) of 25 patients were removed. In each Total RNA was prepared with the Ultraspec RNA Isola- brain region examined, RNA exclusion was similarly dis- tion System (Biotecx Laboratories, Houston, Tex), based tributed among the different CDR categories. on the acid guanidinium thiocyanate-phenol-chloroform method.22 STATISTICS RIBONUCLEASE PROTECTION ASSAY Data were analyzed by analysis of variance (ANOVA) com- bined with a post hoc Dunnett multiple comparison test Total RNA was assayed with the RiboQuant Multiprobe to compare each experimental group with the control group. RNase (ribonuclease) Protection Assay System (PharMin- Correlation analysis was performed by calculating the Pear- gen, San Diego, Calif). A custom probe set containing son R coefficient. cal progression of AD dementia. The current study is the RESULTS first to examine the mRNA expression patterns of several inflammatory cytokines in different brain regions as a func- tion of the clinical progression of AD. PATIENT POPULATION It has been suggested that the neuropathological fea- tures of AD occur in different brain areas in a predict- Patient information for this study is summarized in able temporal pattern during the course of the disease Table 1. Extraneous factors that might influence cyto- progression.16 Therefore, cytokines were measured in the kine gene expression were similar across all groups. Cy- entorhinal cortex (Brodmann area [BM] 36/38) and su- tokine mRNA degradation is a concern with long post- perior temporal gyrus (BM 22), 2 brain areas affected in mortem delays. The ANOVA indicated that there were AD, and in the occipital cortex (BM 17), an area that is no significant differences (P..05) among the different less affected in AD. In this study, we determined the pat- CDR groups with respect to postmortem intervals (data tern of cytokine gene expression as a function of AD clini- not shown). Furthermore, all groups had a statistically cal dementia and the neuropathological features of AD similar (P..05) age at death (data not shown). Cyto- and discussed the relevance of these findings to the de- kine expression can also be impacted by antemortem sign of anti-inflammatory drug trials in AD. inflammatory conditions that may require anti- (REPRINTED) ARCH NEUROL / VOL 57, AUG 2000 WWW.ARCHNEUROL.COM 1154 ©2000 American Medical Association.
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]
  • 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]
  • 2Nd Neurological Disorders Summit Program
    Scientific NDS-2016 UNITED Group Program 2nd Neurological Disorders Summit September 07-09, 2016 Venue The DoubleTree by Hilton Baltimore-BWI Airport Hotel Baltimore, MD, USA Day 1 September 07, 2016 08:00-08:45 Registrations @ Pre-Function Area 08:45-09:00 Introduction to NDS-2016 Moderator: Rajendra Badgaiyan, University of Minnesota, USA Keynote Session @ Annapolis | Harbor Advances in Neuroimaging and Their Application to Schizophrenia and Mild 09:00-09:35 Traumatic Brain Disorder Martha Shanton, Harvard Medical School, USA Mitochondrial Transport: New Insights and Implications in Neuronal Degeneration 09:35-10:10 and Regeneration Zu-Hang Sheng, NIH/NINDS, USA Synesthesia and the Creative Spark 10:10-10:45 Richard E Cytowic, George Washington University, USA 10:45-11:00 Coffee Break & Book Signing by Richard E Cytowic @ Main Hallway At the Crossroads between Promotion of Health and Prevention of Age-Related 11:00-11:35 Neurodegeneration with Natural Drugs to Avoid the Catastrophic Cliff of Neuronal Failure Giulio Maria Pasinetti, Icahn School of Medicine at Mount Sinai, USA Opioid Reward Mechanism: A Potential Role in Metabolic Disturbances? 11:35-12:10 Igor Elman, Wright State University, USA First Case of Brain Protection in Out of Hospital Cardiac Arrest 12:10-12:45 Guy Hugues Fontaine, Pierre-and-Marie-Curie University, France 12:45-13:40 Lunch Break @ Edens Landing Hypothesizing that Neuropharmacological and Neuroimaging Studies of Glutaminergic- Dopaminergic Optimization Complex (KB220Z) are Indicative of Producing “Dopamine
    [Show full text]