Affiliation:
1. Department of Neurology Icahn School of Medicine at Mount Sinai New York NY 10029 USA
2. Nash Family Department of Neuroscience Icahn School of Medicine at Mount Sinai 1 Gustave L. Levy Place New York NY 10029 USA
3. Depression and Anxiety Center for Discovery and Treatment Department of Psychiatry Icahn School of Medicine at Mount Sinai 1 Gustave L. Levy Place New York NY 10029 USA
4. Geriatric Research Education and Clinical Center James J. Peters Veterans Affairs Medical Center Bronx NY 10468 USA
Abstract
ScopeThe goal of this study is to investigate the effects of a bioactive dietary polyphenol preparation (BDPP), which is made up of grape‐derived polyphenols, on microglial responses, as well as the underlying molecular mechanisms in depression and anxiety‐like behaviors.Methods and resultsThe study finds that treatment with BDPP significantly decreases depression‐like and anxiety‐like behaviors induced by chronic stress in mice, while leaving their locomotor activity unaffected. The study also finds that BDPP treatment reverses microglia activation in the amygdala and hippocampal formation, regions of the brain involved in emotional regulation, from an amoeboid shape to ramified shape. Additionally, BDPP treatment modulates the release of pro‐inflammatory cytokines such as interleukin‐6 via high mobility box 1 protein and the receptor for advanced glycation end products (HMGB1‐RAGE) signaling pathway in activated microglia induced by chronic stress.ConclusionThe findings suggest regional heterogeneity in microglial responses following chronic stress in subregions of the corticolimbic circuit. Specifically, activation of the immune‐inflammatory HMGB1‐RAGE pathway may provide a new avenue for preventing the manifestation of psychiatric impairments including stress‐induced anxiety‐ and depression‐like behavior, using bioactive and bioavailable polyphenols.
Funder
National Center for Complementary and Integrative Health
U.S. Department of Veterans Affairs
Subject
Food Science,Biotechnology