Experts review the critical interaction of neuroimmune communication and brain plasticity in a special issue of <em>Brain Plasticity</em>
Research over the last five decades has consolidated our understanding of the critical roles of neuroimmune communication in the maintenance of homeostasis and in the pathogenesis of peripheral and central nervous system related diseases.
“In vital peripheral organs, hyper-expression of proinflammatory cytokines after viral infection such as COVID-19 often results in significant immune mediated damage, turning the body’s defense mechanism into a cause of its demise,” explained Guest Editors Tal Burstyn-Cohen, PhD, Institute for Oral and Biomedical Research (IBOR), Faculty of Dental Medicine, The Hebrew University, Jerusalem, Israel; and Ning Quan, PhD, Department of Biomedical Science, Charles E. Schmidt College of Medicine, Stiles-Nicholson Brain Institute, Florida Atlantic University, Jupiter, FL, USA. “The survivors of COVID-19 also show long-haul mental health disorders, likely caused by the long lasting secondary cytokine storm that ensues in the central nervous system – reflected in the title of this special issue.”
Ruth M. Barrientos, PhD, and Stephanie M. Muscat, PhD candidate, both of The Ohio State University, review accumulated evidence for the “perfect cytokine storm” that explains how immune activation initiated in the periphery might sensitize microglial cells of the brain to translate peripheral cytokine storm into a central menace, especially in the elderly. Behind the usually protective blood brain barrier, microglial senescence, high-fat diet, surgical trauma, oxidative stress, psychological stress, and compromised blood brain barrier prime the vulnerability of the central nervous system, allowing a significant peripheral infectious event to tip the system into a prolonged state of dysfunction.
Ning Quan, PhD, Florida Atlantic University, and Daniel P. Nemeth, BS, The Ohio State University, provide an update on the current understanding of a crucial cytokine in this brain cytokine storm, interleukin-1 (IL-1), which modulates neural networks. Distinct neuroimmune effects mediated by IL-1 can now be analyzed on a cell type-specific basis, heralding in new paradigms to explain how this pivotal cytokine might regulate neural network activity.
Tal Burstyn-Cohen, PhD, and Arielle Hochberg, MSc, both of The Hebrew University, review the multifarious roles fulfilled by Tyro3, Axl and Mertk (known collectively as TAM) receptors when the central nervous system experiences a cytokine storm and also under the calmness of healthy homeostasis. Expressed by microglia – the immune cells of the central nervous system – TAMs perform bona fide immune-related roles as regulation of inflammation and cytokine secretion both in health and in disease. An overview of the recent studies examining the roles of TAM-signaling molecules in disease includes models of Alzheimer’s and Parkinson’s disease, ischemia, and multiple sclerosis.
Alexander D. Walsh, PhD candidate, The Florey Institute of Neuroscience and Mental Health, and colleagues take a closer look into the transcriptional regulation of the TAM receptor MERTK. MERTK expression is enriched in the central nervous system and in resident innate immune cells where it regulates numerous functions that support brain plasticity. Polymorphisms in the MERTK gene are associated with multiple sclerosis. These data may advance strategies to therapeutically intervene and regulate MERTK transcription in various disease states to tailor inflammatory signaling and efferocytosis, which may affect multiple aspects of brain plasticity.
“Two emerging areas are in the field are direct modulation of neural circuitry via cytokine receptors expressed on neurons and the impact of immunosuppressive signaling on neuronal functions,” noted Dr. Quan. “Scientists must carefully examine how immune system molecules operate in the brain because entirely new modalities might exist for these molecules to exert different functions in the brain. Understanding these issues is highly important at this time as we learn that immune response, for example towards COVID-19, could profoundly influence mental health even after the patients have recovered from the infection.”
“Immune cells are active players in brain physiology, but much remains to be discovered about the effects of the immune cells on brain plasticity, how systemic immune signals are interpreted and sensed by the brain, and how these affect brain function,” added Dr. Burstyn-Cohen.
Looking forward, the field is still lacking good markers to distinguish between brain and circulating immune cells, especially to distinguish between microglia and peripheral monocytes/macrophages in cases where the blood-brain barrier is breached. Research also needs to improve in vivo monitoring of immune status and develop non-invasive early detection of disease and inflammatory markers. “We hope the articles in this issue help us to continue this journey,” concluded the Guest Editors.
NOTES FOR EDITORS
Open Access Special Issue: The Immune System and Brain Function
Brain Plasticity, Volume 7, Issue 1
Guest Editors: Tal Burstyn-Cohen and Ning Quan
Full issue: content.iospress.com/journals/brain-plasticity/7/1
Contact Diana Murray, IOS Press (+1 718-640-5678, firstname.lastname@example.org) for additional information. Journalists wishing to interview the Guest Editors or contributing authors should contact Tal Burstyn-Cohen (email@example.com) or Ning Quan (firstname.lastname@example.org).
About Brain Plasticity
Brain Plasticity publishes peer-reviewed original articles, reviews, and short communications on all aspects of neurogenesis, gliogenesis, and synaptic plasticity, from development to the adult. This includes research articles or reviews on modifications to neural circuits in the developing and adult brain, whether by learning or physical activity, spine formation, changes in neural structure, changes in neural networks, new cell division, as well as response of the CNS to experimental injuries, neurodevelopmental and neurodegenerative disorders. Papers adopting fresh conceptual approaches on specification and function at the molecular and cellular levels, neural circuits, systems and behavioral levels are encouraged. iospress.com/brain-plasticity
About IOS Press
IOS Press is an independent international scientific, technical, medical (STM) publishing house established in 1987 in Amsterdam. We produce around 90 journals and 70 books annually in a broad range of subject categories, primarily specializing in biomedical and life sciences (including neurosciences, medical informatics, cancer research, rehabilitation) and physical sciences (including computer sciences, artificial intelligence, engineering). In addition, we offer specialized services that support scientific advancement. iospress.com