Daily Alcohol Intake Triggers Aberrant Synaptic Pruning Leading to Synapse Loss and Anxiety-Like Behavior
Abstract
Introduction
Alcohol abuse has detrimental cognitive and behavioral consequences. Binge alcohol use activates resident phagocytic immune cells in the brain called microglia in mice and is associated with anxiety in humans. Socodato et al. found that a binge alcohol use protocol in male mice induced microglia to selectively scavenge excitatory synapses between neurons in the prefrontal cortex. The loss of these connections did not cause neuronal death during the study but instead depressed neurotransmission and increased anxiety-like behaviors in the mice. These findings suggest that binge alcohol use induces anxiety by activating microglia that destroy neuronal connections.
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.
Method
The researchers gave an alcohol solution to male mice, equivalent to 10 days of binge alcohol use to simulate chronic binge alcohol use.
Results
This research found that a protocol simulating chronic binge alcohol use 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.
Conclusion
The data in this research suggest that aberrant pruning of excitatory synapses by microglia may disrupt synaptic transmission in response to alcohol abuse.
Implications
This study analyses the immediate effects binge alcohol use has on the brain.
The simulated chronic binge alcohol use spurred immune cells in mice brains to destroy the synapses — or connections — between neurons, leading to anxiety and other cognitive issues.
Even for a short period of time, excessive [alcohol use] is likely to affect the brain, increasing the level of anxiety, a relevant feature in alcohol abuse and addiction,” said João Relvas, co-author of the study from the University of Porto, as per Voa News.
João Relvas, co-author of the study from the University of Porto.
The study showed that effects of binge alcohol use is underestimated. The results show that binge alcohol use can seriously affect the brain specifically for young people. It is important that policies to delay and reduce initiation to alcohol and awareness for young people are prioritized.