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Binge ethanol exposure induces endoplasmic reticulum stress in the brain of adult mice.


ABSTRACT: Alcohol abuse causes brain damage and cognitive dysfunction. However, the underlying mechanisms remain elusive. Endoplasmic reticulum (ER) acts as machinery to ensure the proper folding of newly synthesized proteins. The perturbation of ER, i.e., ER stress, plays a pivotal role in some neurological disorders. Mammalian target of rapamycin (mTOR), a serine/threonine kinase, is involved in the regulation of ER stress. The current study sought to determine whether binge ethanol exposure induces ER stress in adult mouse brain and the role mTOR signaling during this process. Adult C57BL6 mice received binge ethanol exposure by daily gavage (5?g/kg, 25% ethanol w/v) for 1, 5 or 10?days. Binge ethanol exposure caused neurodegeneration and neuroinflammation after 5?days of exposure, and a concomitant increase of ER stress and inhibition of mTOR. However, ethanol exposure did not significantly alter spatial learning and memory, and spontaneous locomotor activity. Ethanol treatment induced ER stress and the death of cultured neuronal cells. Cotreatment with an ER stress inhibitor, sodium 4-phenylbutyrate (4-PBA) significantly diminished ethanol-induced ER stress and neuronal apoptosis, suggesting that ER stress contributes to ethanol-induced neurodegeneration. Furthermore, the blockage of mTOR activity by rapamycin increased ER stress in cultured neuronal cells; whereas the activation or inhibition of ER stress by tunicamycin or 4-PBA respectively had little effects on mTOR signaling. These results suggested that mTOR signaling is upstream of ER stress and may thereby mediate ethanol-induced ER stress.

SUBMITTER: Wang Y 

PROVIDER: S-EPMC6258015 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Binge ethanol exposure induces endoplasmic reticulum stress in the brain of adult mice.

Wang Yongchao Y   Wang Xin X   Li Hui H   Xu Mei M   Frank Jacqueline J   Luo Jia J  

Toxicology and applied pharmacology 20180813


Alcohol abuse causes brain damage and cognitive dysfunction. However, the underlying mechanisms remain elusive. Endoplasmic reticulum (ER) acts as machinery to ensure the proper folding of newly synthesized proteins. The perturbation of ER, i.e., ER stress, plays a pivotal role in some neurological disorders. Mammalian target of rapamycin (mTOR), a serine/threonine kinase, is involved in the regulation of ER stress. The current study sought to determine whether binge ethanol exposure induces ER  ...[more]

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2015-01-01 | GSE53975 | GEO