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Activation of gamma-aminobutyric Acid (A) Receptor Protects Hippocampus from Intense Exercise-induced Synapses Damage and Apoptosis in Rats
Ding, Yi; Xie, Lan; Chang, Cun-Qing; Chen, Zhi-Min; Ai, Hua
关键词Endoplasmic Reticulum Stress-induced Apoptosis gamma-aminobutyric Acid (A) Receptor Hippocampus Intense Exercise Synapse Plasticity
刊名CHINESE MEDICAL JOURNAL
2015-09-05
DOI10.4103/0366-6999.163392
128期:17页:2330-2339
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Medicine, General & Internal
研究领域[WOS]General & Internal Medicine
关键词[WOS]STRESS-INDUCED APOPTOSIS ; GABA-RECEPTORS ; NMDA ; SYNAPTOPHYSIN ; STIMULATION ; PLASTICITY ; ISCHEMIA ; MUSCIMOL ; MORPHINE ; NEURONS
英文摘要

Background: Our previous study has confirmed that one bout of exhaustion (Ex) can cause hippocampus neurocyte damage, excessive apoptosis, and dysfunction. Its initial reason is intracellular calcium overload in hippocampus triggered by N-methyl-D-aspartic acid receptor (NMDAR) over-activation. NMDAR activation can be suppressed by gamma-aminobutyric acid (A) receptor (GABA(A)R). Whether GABA(A)R can prevent intense exercise-induced hippocampus apoptosis, damage, or dysfunction will be studied in this study.

Methods: According to dose test, rats were randomly divided into control (Con), Ex, muscimol (MUS, 0.1 mg/kg) and bicuculline (BIC, 0.5 mg/kg) groups, then all rats underwent once swimming Ex except ones in Con group only underwent training. Intracellular free calcium concentration ([Ca2+]i) was measured by Fura-2-acetoxymethyl ester; glial fibrillary acidic protein (GFAP) and synaptophysin (SYP) immunofluorescence were also performed; apoptosis were displayed by dUTP nick end labeling (TUNEL) stain; endoplasmic reticulum stress-induced apoptosis pathway was detected by Western blotting analysis; Morris water maze was used to detect learning ability and spatial memory.

Results: The appropriate dose was 0.1 mg/kg for MUS and 0.5 mg/kg for BIC. Ex group showed significantly increased [Ca2+]i and astrogliosis; TUNEL positive cells and levels of GFAP, B cell lymphoma-2 (Bcl-2) associated X protein (Bax), caspase-3, caspase-12 cleavage, CCAAT/enhancer binding protein homologous protein (CHOP), and p-Jun amino-terminal kinase (p-JNK) in Ex group also raised significantly compared to Con group, while SYP, synapse plasticity, and Bcl-2 levels in Ex group were significantly lower than those in Con group. These indexes were back to normal in MUS group. BIC group had the highest levels of [Ca2+]i, astrogliosis, TUNEL positive cell, GFAP, Bax, caspase-3, caspase-12 cleavage, CHOP, and p-JNK, it also gained the lowest SYP, synapse plasticity, and Bcl-2 levels among all groups. Water maze test showed that Ex group had longer escape latency (EL) and less quadrant dwell time than Con group; all indexes between MUS and Con groups had no significant differences; BIC had the longest EL and least quadrant dwell time among all groups.

Conclusions: Activation of GABA(A)R could prevent intense exercise-induced synapses damage, excessive apoptosis, and dysfunction of hippocampus.

语种英语
WOS记录号WOS:000361746700011
项目编号30270636 ; 30671015
资助机构National Nature Science Foundation of China
引用统计
被引频次:3[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/60487
专题北京大学临床肿瘤学院_药剂科
北京大学第三临床医学院_运动医学研究所
作者单位Peking Univ, Hosp 3, Inst Sports Med, Beijing 100191, Peoples R China
推荐引用方式
GB/T 7714
Ding, Yi,Xie, Lan,Chang, Cun-Qing,et al. Activation of gamma-aminobutyric Acid (A) Receptor Protects Hippocampus from Intense Exercise-induced Synapses Damage and Apoptosis in Rats[J]. CHINESE MEDICAL JOURNAL,2015,128(17):2330-2339.
APA Ding, Yi,Xie, Lan,Chang, Cun-Qing,Chen, Zhi-Min,&Ai, Hua.(2015).Activation of gamma-aminobutyric Acid (A) Receptor Protects Hippocampus from Intense Exercise-induced Synapses Damage and Apoptosis in Rats.CHINESE MEDICAL JOURNAL,128(17),2330-2339.
MLA Ding, Yi,et al."Activation of gamma-aminobutyric Acid (A) Receptor Protects Hippocampus from Intense Exercise-induced Synapses Damage and Apoptosis in Rats".CHINESE MEDICAL JOURNAL 128.17(2015):2330-2339.
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