Friday, October 02, 2020

Tipsy microglia binge on synapses - another reason to cut down on the booze

Socodato et al. find that binge-level alcohol intake (about five drinks for an average person) over 10 consecutive days enhances Src-to–tumor necrosis factor (TNF) signaling in prefrontal cortex microglia, which boosts their engulfment capacity and leads to aberrant synaptic pruning, culminating in synapse loss and anxiety-like behavior. Overall, their data suggest that aberrant synaptic pruning by microglia might play an important role in the synaptic transmission deficits elicited by alcohol abuse. Their abstract:
Alcohol abuse adversely affects the lives of millions of people worldwide. Deficits in synaptic transmission and in microglial function are commonly found in human alcohol abusers and in animal models of alcohol intoxication. Here, we found that a protocol simulating chronic binge drinking in male mice resulted in aberrant synaptic pruning and substantial loss of excitatory synapses in the prefrontal cortex, which resulted in increased anxiety-like behavior. Mechanistically, alcohol intake increased the engulfment capacity of microglia in a manner dependent on the kinase Src, the subsequent activation of the transcription factor NF-κB, and the consequent production of the proinflammatory cytokine TNF. Pharmacological blockade of Src activation or of TNF production in microglia, genetic ablation of Tnf, or conditional ablation of microglia attenuated aberrant synaptic pruning, thereby preventing the neuronal and behavioral effects of the alcohol. Our data suggest that aberrant pruning of excitatory synapses by microglia may disrupt synaptic transmission in response to alcohol abuse.

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