The Role of Innate Immunity in Neurological Disorders

Neuroinflammation is a major contributor to the pathophysiology of a variety of nervous system disorders.

The innate immune system is an important mechanism that engages microglia, leads to neuroinflammation, and underlies clinical problems ranging from neurodevelopmental disorders to neurodegenerative diseases. Understanding how microglia develop and act in the brain and the pathways by which they cause neuroinflammation is a primary goal for finding treatments for such diseases.

This Neurobiology of Disease Workshop, held at Neuroscience 2018, reveals ways in which neuroinflammation contributes to the pathophysiology of disorders of the central nervous system.

Topics covered include:

• Transcriptional regulatory mechanisms involved in microgliogenesis and activation.
• The role of microglia in synaptic and cognitive decline, including in schizophrenia.
• Pathways to neurodegeneration as in Alzheimer’s, including how microglial interactions contribute to progression of the disease, and similar neuroinflammatory responses.
• Innate immune responses in depression and other psychiatric disorders.
• Neuroimmune interactions that drive chronic itch conditions.
• How traumatic brain injury can change cognition and lead to disorders associated with deficits in impulse control, including addiction.

*This event was organized by Gwenn Garden, Stuart Lipton, and John Neumaier. Josep Dalmau gave a patient presentation.

Speakers

Chris Glass, MD, PhD

Chris Glass is a professor of cellular and molecular medicine and of medicine at the University of California, San Diego. He has a long-standing interest in elucidating the molecular mechanisms by which sequence-specific transcription factors, co-activators, and co-repressors regulate the development and function of macrophages in health and disease. His current studies use a combination of genetics and genomics to define molecular mechanisms specifying transcriptional regulatory elements that establish macrophage identity and cell-specific responses to environmental signals. Glass’ laboratory is applying these approaches to understand pathological programs of macrophage gene expression that promote the development of atherosclerosis, diabetes, cancer, and neurodegenerative diseases.

Beth Stevens, PhD

Beth Stevens is an associate professor at Harvard Medical School, in the FM Kirby Neurobiology Center at Boston Children’s Hospital. Her research focuses on the mechanisms regulating the disappearance of synapses by focusing on how immune-related molecules mediate this process. Through her most recent work, she seeks to uncover the role that microglial cells, the immune cells of the central nervous system, and their connectivity play in neurodevelopmental and neuropsychiatric disorders. She and her team identified how microglia affect synaptic pruning, a critical developmental process of cutting back on synapses, problems with which are hypothesized to contribute to developmental disorders such as schizophrenia and autism. In addition, her work is providing novel insight into the mechanisms by which microglia contribute to synaptic and cognitive dysfunction in neurodegenerative diseases, including Alzheimer’s, that could lead to new therapies and biomarkers. Stevens was named a MacArthur Fellow in 2015 and shared the National Alliance on Mental Illness (NAMI) Research Award with Steven McCarrolla and Michal Carroll in 2016. She is a member of the Broad Institute and the Stanley Center for Neuropsychiatric Research.

Joseph El-Khoury, MD

Joseph El-Khoury is an associate professor of medicine at Harvard Medical School and a physician in the Infectious Disease Division and the Center for Immunology and Inflammatory Diseases at Massachusetts General Hospital. He investigates the role of the innate immune system in neurodegeneration, inflammation, and host defense against infectious pathogens. El Khoury has made several seminal contributions to the field of neuroimmunology, including identifying microglial receptors for amyloid β, defining the microglial transcriptome and sensome, and identifying pathways mediating monocyte recruitment into the brain. He is an associate editor of JNeurosci and a member of the National Scientific Advisory Council of the American Federation for Aging Research. He is currently funded by the National Institute of Aging and the National Institute of Allergy and Infectious Diseases.

Andrew Miller, MD

Andrew H. Miller is the William P. Timmie Professor and vice chair for research in the Department of Psychiatry and Behavioral Sciences at the Emory University School of Medicine. He is an internationally recognized expert in interactions between the brain and immune system as they relate to depression. His work has demonstrated that during immune activation, inflammatory cytokines can access the brain and interact with the metabolism of dopamine and glutamate, while altering neurocircuits relevant to motivation and reward as well as anxiety and alarm. Additionally, Miller and his group conducted the first clinical trial examining the efficacy of an immunotherapy (cytokine antagonist) for the treatment of depression. He has produced more than 250 scholarly publications, won numerous research, teaching, and mentoring awards, and is a Board-Certified Psychiatrist voted as a Top Doctor in Psychiatry for the past three years.

Diana Bautista, PhD

Diana Bautista is a HHMI Investigator and professor at the University of California, Berkeley. Bautista’s research aims to decipher the neuroimmune interactions underlying itch, pain and inflammation. She received her undergraduate degree in Biology from the University of Oregon and her PhD in Neuroscience from Stanford University. She completed her postdoctoral training with David Julius at University of California, San Francisco.

Catharine Winstanley, PhD

Catharine Winstanley is a behavioral neuroscientist at the University of British Columbia. She is a professor in the Department of Psychology and an associate member of the Division of Neurology. Her research is focused on understanding the neurobiological regulation of cognitive traits such as impulsivity and decision-making, with the goal of using this knowledge to improve treatments for psychiatric disorders such as problem gambling and drug addiction.