Neuroscience and Immunology: Intersection Yields Clues for the Etiology of Psychiatric and Neurodegenerative Diseases
Two strong and rapidly growing disciplines, neuroscience and immunology, each have made substantial scientific achievements. Yet the two rarely find a common language and purpose necessary to support scientific breakthroughs. A growing number of reports in the past 10 years may finally change this status quo as the interplay between immunology and neuroscience comes into focus. Coming from the study of a variety of seemingly disparate diseases, elements that were previously considered to be domains of one discipline are now discovered in the other. Examples include synapses made by T cells, and cytokines as neuromodulators.
This symposium, Neuroscience and Immunology: Intersection Yields Clues for the Etiology of Psychiatric and Neurodegenerative Diseases, held at the New York Academy of Sciences on October 26, 2010, provided an introduction to the interdisciplinary field of neuroimmunology and presents a compelling case for the role of specific inflammatory cytokines in sickness behavior and in clinical depression. Additional topics included how cytokines mediate the stress response at molecular, cellular, and systems levels; the molecular mechanisms of cellular stress in Alzheimer's disease; and pro-inflammatory signaling's role in amyloid-beta peptide-mediated neuronal dysfunction and memory impairment. Research was presented that identified the neurotoxic mechanisms and transduction pathways that are associated with TNFα signaling. Presenters discussed modulating glial reactivity and inflammatory cytokines as a possible therapeutic strategy against neurodegenerative diseases, and they unveiled recent discoveries on specific receptors for fibrinogen that advance our understanding of its role as a clotting factor, a regulator of inflammation, and many functions in between.
Andrew Miller from Emory University School of Medicine provided an introduction to the interdisciplinary field of neuroimmunology and began with an overview of depression, which affects 9% of the population in the U.S. Of these, around one third, or around 9 million people, are resistant to or intolerant of conventional antidepressant therapies. He provided an outline of inflammation as a common mechanism of diseases, including neuropsychiatric disorders such as major depression, and he went on to present a compelling case for the role of specific inflammatory cytokines in this mechanism. Building on the description of cytokines' myriad roles in normal and pathological cell functioning, Raz Yirmiya from Hebrew University then elaborated on how cytokines, such as interleukin 1 (IL-1) mediate the stress response at molecular, cellular, and systems levels. He discussed studies from the last two decades that demonstrate that inflammatory cytokines in the brain mediate the detrimental effects of chronic stress, infections, and autoimmune and neurodegenerative diseases on memory functioning and mood. Such harm mitigation occurs particularly through microglial activation and the production of pro-inflammatory cytokines such as IL-1, and works especially against damage to hippocampal-dependent memory that might ordinarily occur as a result of chronic stress or disease.
Shi Du Yan from Columbia University then discussed the molecular mechanisms of cellular stress in Alzheimer's disease and considered how pro-inflammatory signaling plays a role in amyloid-beta peptide-mediated neuronal dysfunction and memory impairment. Great detail was provided concerning RAGE, a receptor for advanced glycation end-products. RAGE is an immunoglobulin-like cell surface receptor that is often described, in reference to the structural heterogeneity of its ligand, as a pattern recognition receptor. RAGE inhibitors hold great potential for significant therapeutic advances against Alzheimer's disease in the near future. Malú Tansey from Emory University School of Medicine captivated the audience with a description of her research identifying the neurotoxic mechanisms and transduction pathways associated with tumor necrosis factor (TNF) signaling. She explained potential therapeutic strategies for neurodegenerative diseases, strategies that involve altering glial reactivity and adjusting inflammatory cytokines. Katerina Akassoglou from Gladstone Institute & UCSF discussed studies in animal models that have demonstrated that extravascular fibrinogen can contribute to inflammatory diseases such as multiple sclerosis, rheumatoid arthritis, and myocardial infarction. She illustrated her presentation with some movies from animal model studies of multiple sclerosis. These studies have demonstrated that fibrinogen is not merely a marker of BBB (blood–brain barrier) disruption, but also a mediator of neuroinflammation, both of which have known links to neurological disease initiation.
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Seongeun (Julia) Cho, PhD
U.S. Food and Drug Administration
Ken Jones, PhD
Lundbeck Research USA
Lars Pedersen, PhD
Lundbeck Research USA
Jennifer Henry, PhD
The New York Academy of Sciences
Katerina Akassoglou, PhD
Katerina Akassoglou performed her graduate studies at the University of Athens in Greece and the University of Vienna in Austria, where she developed a novel transgenic animal model for multiple sclerosis. Akassoglou performed her postdoctoral studies at SUNY at Stony Brook and the Rockefeller University. Following research associate positions at Rockefeller University and New York University, she became assistant professor of pharmacology at the University of California, San Diego in 2003. Since 2008, she has been an associate professor of neurology at the University of California, San Francisco and an associate investigator at the Gladstone Institute of Neurologic Disease.
Andrew Miller, MD
Andrew Miller is William P. Timmie Professor of Psychiatry and Behavioral Sciences and Director of Psychiatric Oncology at the Winship Cancer Institute at the Emory University School of Medicine in Atlanta, Georgia. Miller attended medical school at the Medical College of Georgia and did a residency in psychiatry at the Albert Einstein College of Medicine. As a junior faculty member, Miller trained at Mount Sinai School of Medicine and Rockefeller University in New York. Miller is a Board Certified Psychiatrist and past examiner for the American Board of Psychiatry and Neurology.
Malú Tansey, PhD
Malú Gámez Tansey obtained her BS/MS in Biological Sciences from Stanford University and her PhD in Physiology from The University of Texas Southwestern Graduate School in Dallas. She is a tenured Associate Professor of Physiology and a member of the Center for Neurodegenerative Disease (CND) at Emory University School of Medicine in Atlanta, Georgia. Her research is supported with grants from The Michael J. Fox Foundation for Parkinson's Research, the National Parkinson Foundation, the American Health Assistance Foundation, the HighQ/CHDI Foundation, and the National Institutes of Health (NIH).
Shi Du (Shirley) Yan, MD, MS
Shi Du Yan is a Professor, Department of Pathology and Surgery, Taub Institute for Research on Alzheimer's disease and the Aging Brain, Columbia University, New York. Yan's research focuses on investigating cellular and molecular mechanisms of cell stress and survival in neurodegenerative disorders relevant to Alzheimer's disease. Yan has authored 140 publications. Her research project is supported by National Institute of Health and Alzheimer Association. She received several awards including the Zenith Fellow Award from the Alzheimer's Association in 2005. She is an active member of the scientific review committee for NIH, VA merit grant, Alzheimer's association, and other foundation grants.
Raz Yirmiya, PhD
Raz Yirmiya holds a PhD in Neuroscience from UCLA. He is currently a Professor and director of the Inter-Departmental Program in Psychobiology at the Hebrew University of Jerusalem, Israel. He investigates the implications of immune-to-brain communication for psychiatric and neurological conditions. Yirmiya edited two books and published more than 145 papers in prestigious journals, including Nature Medicine, PNAS, Journal of Neuroscience, Molecular Psychiatry, Archives of General Psychiatry, Annals of Neurology, Biological Psychiatry, and Brain, Behavior and Immunity. He is currently the president of the PsychoNeuroImmunology Research Society (PNIRS) and an Associate Editor of Brain, Behavior and Immunity.