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学科主题: 临床医学
题名:
Effects of diet on adenosine monophosphate-activated protein kinase activity and disease progression in an amyotrophic lateral sclerosis model
作者: Zhao, Zichun; Sui, Yanling; Gao, Wenchao; Cai, Bin; Fan, Dongsheng
关键词: Amyotrophic lateral sclerosis ; metabolism ; adenosine monophosphate-activated protein kinase ; heat shock protein-70 ; calorie restriction ; high-fat diet
刊名: JOURNAL OF INTERNATIONAL MEDICAL RESEARCH
发表日期: 2015-02-01
DOI: 10.1177/0300060514554725
卷: 43, 期:1, 页:67-79
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Medicine, Research & Experimental ; Pharmacology & Pharmacy
研究领域[WOS]: Research & Experimental Medicine ; Pharmacology & Pharmacy
关键词[WOS]: LIFE-SPAN ; NEURONAL SURVIVAL ; MOUSE MODEL ; MICE ; ENERGY ; AMPK ; ALS
英文摘要:

Objectives To study the effects of diet on disease progression and activity levels of adenosine monophosphate-activated protein kinase (AMPK), and its downstream targets, in an amyotrophic lateral sclerosis (ALS) animal model.

Methods AMPK activity was measured in cerebral cortex, spinal cord, cerebellum and hindlimb muscle tissue using immunohistochemistry in transgenic mice overexpressing human superoxide dismutase-1 (SOD1(G93A)) fed a high-fat (HFD), standard ad libitum (AL) or calorie-restricted (CR) diet; AMPK activity was also measured in wild-type (SOD1(WT)) mice. Activity of AMPK and phospho-AMPK, acetyl coenzyme-A carboxylase (ACC), phospho-ACC and heat shock protein-70 (Hsp70) were also measured using Western blot. Food intake and grip strength were recorded; body composition was analysed using dual energy X-ray absorptiometry. Motor neuron survival was observed using Nissl staining.

Results AMPK activity increased and Hsp70 expression decreased in AL SOD1(G93A) mice compared with SOD1(WT) mice in spinal cord and hindlimb muscle. Compared with AL SOD1(G93A) mice, CR SOD1(G93A) mice showed increased AMPK activity, downregulated Hsp70 expression, reduced motor neuron survival in spinal cord and hindlimb muscle and reduced lifespan; HFD SOD1(G93A) mice showed opposite effects.

Conclusions In this mouse model, increased AMPK activity seems to play a negative role in motor neuron survival, possibly through a novel mechanism involving Hsp70 downregulation. These changes can be modified by diet. Inhibition of AMPK may provide a therapeutic strategy for ALS.

语种: 英语
所属项目编号: 81030019
项目资助者: National Natural Sciences Foundation of China
WOS记录号: WOS:000349116500008
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/52892
Appears in Collections:北京大学第三临床医学院_神经内科_期刊论文

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作者单位: Peking Univ, Hosp 3, Dept Neurol, Beijing 100191, Peoples R China

Recommended Citation:
Zhao, Zichun,Sui, Yanling,Gao, Wenchao,et al. Effects of diet on adenosine monophosphate-activated protein kinase activity and disease progression in an amyotrophic lateral sclerosis model[J]. JOURNAL OF INTERNATIONAL MEDICAL RESEARCH,2015,43(1):67-79.
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