Its complicated: The relationship between alcohol and microglia in the search for novel pharmacotherapeutic targets for alcohol use disorders

Melbourne, Jennifer K.; Thompson, Keith; Peng, Hui; Nixon, Kimberly

doi:10.1016/bs.pmbts.2019.06.011

Cited by 34 publications

(45 citation statements)

References 272 publications

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“…Whether alcohol-induced microglia loss, dysfunction, or the results of the combination of the two persist in the long term is not known. Signs of microgliosis, as well as effects on neuronal survival and astrogliosis, vary across different points of abstinence as well as with different patterns of exposure (Kelso et al, 2011 ; Marshall et al, 2013 ; Melbourne et al, 2019 ), suggesting that future studies should consider the transient or permanent nature of microglial loss and dystrophic cells caused by ethanol. Furthermore, the complex dynamics between activated microglia and microglial dysfunction are unknown.…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Neuroimmune activation is hypothesized to contribute to alcohol-induced neuropathology and therefore AUD development, especially in adolescents (Chastain and Sarkar, 2014 ; Crews et al, 2016 ). Adolescents often begin experimenting with alcohol despite their greater susceptibility to its damaging effects (Nixon and McClain, 2010 ; Crews et al, 2016 ), therefore determining the impact of alcohol on the neuroimmune system in adolescents vs. adults is critical to our understanding of how AUDs develop (Crews et al, 2016 ; Melbourne et al, 2019 ). The contribution of the neuroimmune system has been inferred from gene expression studies in human tissues and increased expression of microglial markers and chemokines in the brains of post-mortem alcoholics (e.g., Liu et al, 2004 ; He and Crews, 2008 ; Crews et al, 2013 ).…”

Section: Introductionmentioning

confidence: 99%

“…The contribution of the neuroimmune system has been inferred from gene expression studies in human tissues and increased expression of microglial markers and chemokines in the brains of post-mortem alcoholics (e.g., Liu et al, 2004 ; He and Crews, 2008 ; Crews et al, 2013 ). In both adolescent and adult animal models of AUDs, microglia are activated by excessive ethanol consumption (McClain et al, 2011 ; Crews et al, 2013 ; Marshall et al, 2013 ; Peng et al, 2017 ; for review see Crews et al, 2016 ; Melbourne et al, 2019 ) and manipulating neuroimmune signaling drives alcohol consumption in some models (Agrawal et al, 2011 ; Blednov et al, 2011 ). The specific role of microglia, however, has been less clear (Walter and Crews, 2017 ; Warden et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

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Microglia Dystrophy Following Binge-Like Alcohol Exposure in Adolescent and Adult Male Rats

et al. 2020

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Microglia are dynamic cells that have roles in neuronal plasticity as well as in recovery responses following neuronal injury. Although many hypothesize that hyperactivation of microglia contributes to alcohol-induced neuropathology, in other neurodegenerative conditions disruption of normal microglial processes also contributes to neuronal loss, particularly as microglia become dystrophic or dysfunctional. Based on the observation of a striking, abnormal morphology in microglia during binge-like ethanol exposure, the present study investigated the impact of excessive ethanol exposure on microglia number and dystrophic morphology in a model of alcohol dependence that includes neurodegeneration in both adult and adolescent rats. Following 2-and 4-day binge ethanol exposure, the number of microglia was decreased in the hippocampus and the perirhinal and entorhinal cortices of both adult and adolescent rats. Furthermore, a significant number of microglia with a dystrophic morphology were observed in ethanolexposed tissue, accompanied by a significant decrease in brain-derived neurotrophic factor (BDNF) expression in the hippocampus. Together these findings suggest another means by which microglia may contribute to alcohol-induced neurodegeneration, specifically dystrophic microglia and/or loss of microglia may disrupt homeostatic and recovery mechanisms. These results demonstrate that microglia also degenerate with excessive alcohol exposure, which has important implications for understanding the role of microglia-and specifically their contributions to plasticity and neuronal survival-in neurodegenerative disease.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Microglia Dystrophy Following Binge-Like Alcohol Exposure in Adolescent and Adult Male Rats

et al. 2020

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“…The effects of alcohol can vary greatly in relation to the daily amount and type of consumed drink. To date, the adverse effects of alcohol consumption on various parts of the body are known including the cardiovascular system, immune system, liver, intestine, and nervous system [67][68][69][70][71][72][73]. In particular, alcohol is regarded as a negative CNS modulator, since it has been shown that prolonged alcohol consumption can induce neuronal death and impaired brain development [74].…”

Section: Chronic Consumption Of Alcohol and Oligodendrocytesmentioning

confidence: 99%

Environmental and Nutritional “Stressors” and Oligodendrocyte Dysfunction: Role of Mitochondrial and Endoplasmatic Reticulum Impairment

et al. 2020

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Oligodendrocytes are myelinating cells of the central nervous system which are generated by progenitor oligodendrocytes as a result of maturation processes. The main function of mature oligodendrocytes is to produce myelin, a lipid-rich multi-lamellar membrane that wraps tightly around neuronal axons, insulating them and facilitating nerve conduction through saltatory propagation. The myelination process requires the consumption a large amount of energy and a high metabolic turnover. Mitochondria are essential organelles which regulate many cellular functions, including energy production through oxidative phosphorylation. Any mitochondrial dysfunction impacts cellular metabolism and negatively affects the health of the organism. If the functioning of the mitochondria is unbalanced, the myelination process is impaired. When myelination has finished, oligodendrocyte will have synthesized about 40% of the total lipids present in the brain. Since lipid synthesis occurs in the cellular endoplasmic reticulum, the dysfunction of this organelle can lead to partial or deficient myelination, triggering numerous neurodegenerative diseases. In this review, the induced malfunction of oligodendrocytes by harmful exogenous stimuli has been outlined. In particular, the effects of alcohol consumption and heavy metal intake are discussed. Furthermore, the response of the oligodendrocyte to excessive mitochondrial oxidative stress and to the altered regulation of the functioning of the endoplasmic reticulum will be explored.

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Detrimental Effects of Alcohol-Induced Inflammation on Brain Health: From Neurogenesis to Neurodegeneration

et al. 2022

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Its complicated: The relationship between alcohol and microglia in the search for novel pharmacotherapeutic targets for alcohol use disorders

Cited by 34 publications

References 272 publications

Microglia Dystrophy Following Binge-Like Alcohol Exposure in Adolescent and Adult Male Rats

Microglia Dystrophy Following Binge-Like Alcohol Exposure in Adolescent and Adult Male Rats

Environmental and Nutritional “Stressors” and Oligodendrocyte Dysfunction: Role of Mitochondrial and Endoplasmatic Reticulum Impairment

Detrimental Effects of Alcohol-Induced Inflammation on Brain Health: From Neurogenesis to Neurodegeneration

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