Primed for addiction: A critical review of the role of microglia in the neurodevelopmental consequences of adolescent alcohol drinking

Jennifer K. Melbourne, Cassie M. Chandler, Catherine E. Van Doorn, Michael T. Bardo, James R. Pauly, Hui Peng, Kimberly Nixon

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Alcohol is one of the most widely used recreational substances worldwide, with drinking frequently initiated during adolescence. The developmental state of the adolescent brain makes it vulnerable to initiating alcohol use, often in high doses, and particularly susceptible to alcohol-induced brain changes. Microglia, the brain parenchymal macrophages, have been implicated in mediating some of these effects, though the role that these cells play in the progression from alcohol drinking to dependence remains unclear. Microglia are uniquely positioned to sense and respond to central nervous system insult, and are now understood to exhibit innate immune memory, or “priming,” altering their future functional responses based on prior exposures. In alcohol use disorders (AUDs), the role of microglia is debated. Whereas microglial activation can be pathogenic, contributing to neuroinflammation, tissue damage, and behavioral changes, or protective, it can also engage protective functions, providing support and mediating the resolution of damage. Understanding the role of microglia in adolescent AUDs is complicated by the fact that microglia are thought to be involved in developmental processes such as synaptic refinement and myelination, which underlie the functional maturation of multiple brain systems in adolescence. Thus, the role microglia play in the impact of alcohol use in adolescence is likely multifaceted. Long-term sequelae may be due to a failure to recover from EtOH-induced tissue damage, altered neurodevelopmental trajectories, and/or persistent changes to microglial responsivity and function. Here, we review critically the literature surrounding the effects of alcohol on microglia in models of adolescent alcohol misuse. We attempt to disentangle what is known about microglia from other neuroimmune effectors, to which we apply recent discoveries on the role of microglia in development and plasticity. Considered altogether, these studies challenge assumptions that proinflammatory microglia drive addiction. Alcohol priming microglia and there by perturbing their homeostatic roles in neurodevelopment, especially during critical periods of plasticity such as adolescence, may have more serious implications for the neuropathogenesis of AUDs in adolescents.

Original languageEnglish
Pages (from-to)1908-1926
Number of pages19
JournalAlcoholism: Clinical and Experimental Research
Volume45
Issue number10
DOIs
StatePublished - Oct 2021

Bibliographical note

Funding Information:
The authors thank the National Institute on Alcohol Abuse and Alcoholism, the National Institute on Drug Abuse, the National Institute of Neurological Disorders and Stroke for support of R01AA025591 (KN), R21AA025563 (HP/KN), R61NS111081 (JP), T32AA007471 (JKM), and T32DA35200 (CC), and the University of Kentucky College of Pharmacy for funding various works described herein.

Publisher Copyright:
© 2021 by the Research Society on Alcoholism

Keywords

  • EtOH
  • adolescent
  • alcohol
  • microglia
  • neuroimmune

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health

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