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Alcohol and Stress Activation of Microglia and Neurons: Brain Regional Effects
Author(s) -
Walter Thomas Jordan,
Vetreno Ryan P.,
Crews Fulton T.
Publication year - 2017
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.13511
Subject(s) - microglia , corticosterone , sensitization , chronic stress , endocrinology , immune system , medicine , central nervous system , neuroinflammation , premovement neuronal activity , chemistry , immunology , neuroscience , inflammation , psychology , hormone
Background Cycles of alcohol and stress are hypothesized to contribute to alcohol use disorders. How this occurs is poorly understood, although both alcohol and stress activate the neuroimmune system—the immune molecules and cells that interact with the nervous system. The effects of alcohol and stress on the neuroimmune system are mediated in part by peripheral signaling molecules. Alcohol and stress both enhance immunomodulatory molecules such as corticosterone and endotoxin to impact neuroimmune cells, such as microglia, and may subsequently impact neurons. In this study, we therefore examined the effects of acute and chronic ethanol (EtOH) on the corticosterone, endotoxin, and microglial and neuronal response to acute stress. Methods Male Wistar rats were treated intragastrically with acute EtOH and acutely stressed with restraint/water immersion. Another group of rats was treated intragastrically with chronic intermittent EtOH and acutely stressed following prolonged abstinence. Plasma corticosterone and endotoxin were measured, and immunohistochemical stains for the microglial marker CD 11b and neuronal activation marker c‐Fos were performed. Results Acute EtOH and acute stress interacted to increase plasma endotoxin and microglial CD 11b, but not plasma corticosterone or neuronal c‐Fos. Chronic EtOH caused a lasting sensitization of stress‐induced plasma endotoxin, but not plasma corticosterone. Chronic EtOH also caused a lasting sensitization of stress‐induced microglial CD 11b, but not neuronal c‐Fos. Conclusions These results find acute EtOH combined with acute stress enhanced plasma endotoxin, as well as microglial CD 11b in many brain regions. Chronic EtOH followed by acute stress also increased plasma endotoxin and microglial CD 11b, suggesting a lasting sensitization to acute stress. Overall, these data suggest alcohol and stress interact to increase plasma endotoxin, resulting in enhanced microglial activation that could contribute to disease progression.