title: Activated microglia are implicated in cognitive deficits, neuronal death, and successful recovery following intermittent ethanol exposure.
abstract: Microglia function as the primary immune effector cells in the brain and play a pivotal role in the neuroinflammatory processes which are critical component of neurodegenerative diseases. Alcohol abuse has been considered as one of the common reasons for neurodegeneration although the causative factors are poorly understood. Here, we investigated whether activated microglia were implicated in neurodegeneration and cognitive dysfunctions in adult rats after intermittent alcohol abuse. Rats were given orally a priming dose of 5 g/kg ethanol and then 3g/kg every 8h for 4 days, followed by a 3-day ethanol-withdrawal period. These 4 days of ethanol treatments were repeated four times intermittently to simulate the binge drinking of human alcoholics. Neurodegeneration and microglial activation were detected by Fluoro-Jade B staining, Golgi staining, immunohistochemistry and ELISA, respectively, while cognitive function was assessed by Morris water maze and novel object recognition. The results showed that microglial activation and inflammatory cytokine expression were obvious in the parietal association cortex, entorhinal cortex and hippocampus accompanied by neurodegeneration following ethanol treatment. Moreover, learning and memory abilities also declined following ethanol treatments. However, the hypertrophied microglia disappeared accompanied by the decrease of inflammatory cytokines levels on day 4, and ramified microglial proliferated significantly on day 14 after ethanol withdrawal, along with a recovery from neuronal damage and cognitive impairment. Thus, the present study indicated that activated microglia might be involved in neurodegeneration and cognitive dysfunctions induced by intermittent ethanol exposure, and neurotrophic microglia appear to have a contribution to the recovery during abstinence.
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, 110016, Shenyang, PR China.
authors.forename: Ya-Nan
authors.initials: YN
authors.lastname: Zhao
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, 110016, Shenyang, PR China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, 110016, Shenyang, PR China.
authors.forename: Yan-Xia
authors.initials: YX
authors.lastname: Fan
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, 110016, Shenyang, PR China.
authors.forename: Guan-Fang
authors.initials: GF
authors.lastname: Ping
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, 110016, Shenyang, PR China. Electronic address: yangjingyu2006@gmail.com.
authors.forename: Jing-Yu
authors.initials: JY
authors.lastname: Yang
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, 110016, Shenyang, PR China. Electronic address: wucf@syphu.edu.cn.
authors.forename: Chun-Fu
authors.initials: CF
authors.lastname: Wu
mesh_terms: D000818:Animals; D063425:Binge Drinking; D001921:Brain / Q000166:cytology / Q000473:pathology; D016923:Cell Death / Q000187:drug effects*; D002492:Central Nervous System Depressants / Q000097:blood / Q000633:toxicity*; D003072:Cognition Disorders / Q000139:chemically induced* / Q000523:psychology*; D016207:Cytokines / Q000378:metabolism; D049229:Dendritic Spines / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D000431:Ethanol / Q000097:blood / Q000633:toxicity*; D005452:Fluoresceins; D005455:Fluorescent Antibody Technique; D005456:Fluorescent Dyes; D007150:Immunohistochemistry; D008262:Macrophage Activation / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D017628:Microglia / Q000502:physiology*; D009410:Nerve Degeneration; D009474:Neurons / Q000187:drug effects*; D009930:Organic Chemicals; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D021641:Recognition, Psychology / Q000187:drug effects; D020127:Recovery of Function
chemical_list: D002492:Central Nervous System Depressants; D016207:Cytokines; D005452:Fluoresceins; D005456:Fluorescent Dyes; D009930:Organic Chemicals; C435731:fluoro jade; D000431:Ethanol