title: Role of microglia in ethanol-induced neurodegenerative disease: Pathological and behavioral dysfunction at different developmental stages.
abstract: Alcohol abuse can result in significant alterations to the structure of the brain and ultimately to behavioral dysfunctions. Epidemiological studies have shown that alcoholism is closely associated with impaired memory and judgment. However, the degree of deficit (brain injury) depends on factors such as the age of onset, duration of heavy drinking, continuous versus periodic (binge) drinking and the typical amount consumed per session. In recent years, neuroinflammation has been proposed as one of the alcoholism-induced neuropathological mechanisms, since increased levels of microglial markers are observed in the brains of both post-mortem human alcoholics and various alcohol-treated animals, from newborn or adolescent rodents to adult rodents. Many studies have investigated how microglia modulate alcohol-induced behavioral changes such as cognitive deficits, abnormal locomotor activity, motor impairment and mood disturbance. Importantly, we try to characterize and compare the distinct features in different ethanol (EtOH)-induced neurodegenerative disease (NDD) models. Moreover, mounting evidence indicates that in response to certain environmental toxins, microglia can become over-activated under oxidative stress, releasing pro-inflammatory mediators that cause central nervous system (CNS) disease. The molecular mechanisms involve free radical formation and the release of pro-inflammatory cytokines that are detrimental to neighboring neurons and interfere with the molecules regulating cell-cell interactions. The identification and understanding of the cellular and molecular mechanisms of microglial activation are described, as well as multiple downstream targets, in different alcohol-treated animal models. This review might contribute to the development of treatments and/or therapeutic agents that can reduce or eliminate the deleterious effects of alcohol-induced NDD.
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
authors.forename: Jing-Yu
authors.initials: JY
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Biomacromolecules, Insititute of Biophysics, Chinese Academy of Sciences, Beijing 100101, PR China.
authors.forename: Xue
authors.initials: X
authors.lastname: Xue
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, PR China; Department of Pharmacology, Qiqihar Medical University, Qiqihar 161006, PR China.
authors.forename: Hua
authors.initials: H
authors.lastname: Tian
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
authors.forename: Xiao-Xiao
authors.initials: XX
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
authors.forename: Ying-Xu
authors.initials: YX
authors.lastname: Dong
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
authors.forename: Ya-Nan
authors.initials: YN
authors.lastname: Zhao
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
authors.forename: Xue-Chun
authors.initials: XC
authors.lastname: Yao
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cui
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, PR China. Electronic address: wucf@syphu.edu.cn.
authors.forename: Chun-Fu
authors.initials: CF
authors.lastname: Wu
mesh_terms: D000375:Aging / Q000473:pathology / Q000523:psychology; D000437:Alcoholism / Q000150:complications / Q000473:pathology* / Q000523:psychology; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D003071:Cognition / Q000187:drug effects*; D004195:Disease Models, Animal; D000431:Ethanol / Q000633:toxicity*; D006801:Humans; D017628:Microglia / Q000187:drug effects* / Q000473:pathology; D009043:Motor Activity / Q000187:drug effects; D019636:Neurodegenerative Diseases / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology* / Q000523:psychology; D018384:Oxidative Stress / Q000187:drug effects; D012919:Social Behavior
chemical_list: D000431:Ethanol
keywords: Alcohol; Animal models; Behavior; Microglia; Neurodegeneration; Neuroinflammation