Alcohol and Stress Activation of Microglia and Neurons: Brain Regional Effects

Abstract

BackgroundCycles 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.MethodsMale 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 CD11b and neuronal activation marker c‐Fos were performed.ResultsAcute EtOH and acute stress interacted to increase plasma endotoxin and microglial CD11b, 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 CD11b, but not neuronal c‐Fos.ConclusionsThese results find acute EtOH combined with acute stress enhanced plasma endotoxin, as well as microglial CD11b in many brain regions. Chronic EtOH followed by acute stress also increased plasma endotoxin and microglial CD11b, 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.

Stress-induced microglial activation occurs through β-adrenergic receptor: noradrenaline as a key neurotransmitter in microglial activation

“…Using an in vivo rodent model, we demonstrated previously that, upon exposure to acute restraint/water immersion stress, microglia immediately become activated [57]. To our knowledge, this report might be the first one demonstrating stress-induced microglial activation [49, 68], although microglial activation has been reported in various models of acute, subacute, and chronic stress [11, 68, 69]. Regardless of the stress type, it is conceivable that microglia respond to “common” signals generated by stress responses.…”

“…One intriguing feature of microglia is their rapid response to stressful events such as acute [57, 76] or repeated [42, 46, 59, 66] stress, social defeat [35, 52, 72], occlusal teeth disharmony [33], myocardial infarction [48], alcohol [69], sleep deprivation [4, 25], and hypertension [7]. Interestingly, microglial activation is also detected in psychiatric disorders such as depression [65, 75], bipolar disorder [23], and autism [63].…”

Mechanisms of Persistent Neurobiological Changes Following Adolescent Alcohol Exposure: NADIA Consortium Findings

“…). Microglial markers are increased in postmortem brains of humans with AUD (He and Crews, ) and in adult rat brain following AIE (Sanchez‐Alavez et al., ; Walter et al., ). However, these AUD‐ and AIE‐induced changes in microglia are subtle, unlike the dramatic changes following stroke or Alzheimer's disease (Crews et al., ).…”

<p>Psoriasis and alcohol</p>

“…Alcohol has been shown to induce rapid peroxidation of lipids in cerebral vascular smooth muscle cells in rats, which may be a triggering pathway for proinflammatory events in alcohol-induced brain vascular injury 9. It may also activate microglia and neurons in rats 10…”