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

Yongchao Wang; Xin Wang; Hui Li; Mei Xu; Jacqueline Frank; Jia Luo

doi:10.1016/j.taap.2018.08.006

Back

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

Journal article

Open access

Peer reviewed

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

Yongchao Wang, Xin Wang, Hui Li, Mei Xu, Jacqueline Frank and Jia Luo

Toxicology and applied pharmacology, Vol.356(C), pp.172-181

10/01/2018

DOI: 10.1016/j.taap.2018.08.006

PMCID: PMC6258015

PMID: 30114398

Files and links (1)

url

https://doi.org/10.1016/j.taap.2018.08.006View

Published (Version of record) Open Access

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. [Display omitted] •Binge ethanol exposure causes ER stress and neurodegeneration.•Blocking ER stress rescues neurons from ethanol neurotoxicity.•mTOR signaling is involved in ethanol-induced ER stress.

Oxidative Stress

Alcohol use isorder

Brain damage

Endoplasmic reticulum tress

mTOR signaling

Neurodegeneration

Details

Title: Subtitle: Binge ethanol exposure induces endoplasmic reticulum stress in the brain of adult mice
Creators: Yongchao Wang - University of Kentucky
Xin Wang - University of Kentucky
Hui Li - University of Kentucky
Mei Xu - University of Kentucky
Jacqueline Frank - University of Kentucky
Jia Luo - University of Kentucky
Resource Type: Journal article
Publication Details: Toxicology and applied pharmacology, Vol.356(C), pp.172-181
DOI: 10.1016/j.taap.2018.08.006
PMID: 30114398
PMCID: PMC6258015
NLM abbreviation: Toxicol Appl Pharmacol
ISSN: 0041-008X
eISSN: 1096-0333
Publisher: Elsevier Inc
Grant note: DOI: 10.13039/501100003653, name: National Institute of Health, award: AA017226, AA015407; DOI: 10.13039/100000002, name: NIH, award: T32 DK007778; DOI: 10.13039/100000738, name: Department of Veterans Affairs; DOI: 10.13039/100006379, name: Office of Research and Development; DOI: 10.13039/100006190, name: Research and Development, award: BX001721; DOI: 10.13039/100007472, name: University of Kentucky
Language: English
Date published: 10/01/2018
Academic Unit: Pathology
Record Identifier: 9984186678902771

Metrics

20 Record Views

24 Times Cited - Web of Science