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学科主题临床医学
Effects of diet on adenosine monophosphate-activated protein kinase activity and disease progression in an amyotrophic lateral sclerosis model
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
2015-02-01
DOI10.1177/0300060514554725
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
WOS记录号WOS:000349116500008
项目编号81030019
资助机构National Natural Sciences Foundation of China
引用统计
被引频次:10[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/400002259/52892
专题北京大学第三临床医学院_神经内科
作者单位Peking Univ, Hosp 3, Dept Neurol, Beijing 100191, Peoples R China
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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.
APA Zhao, Zichun,Sui, Yanling,Gao, Wenchao,Cai, Bin,&Fan, Dongsheng.(2015).Effects of diet on adenosine monophosphate-activated protein kinase activity and disease progression in an amyotrophic lateral sclerosis model.JOURNAL OF INTERNATIONAL MEDICAL RESEARCH,43(1),67-79.
MLA Zhao, Zichun,et al."Effects of diet on adenosine monophosphate-activated protein kinase activity and disease progression in an amyotrophic lateral sclerosis model".JOURNAL OF INTERNATIONAL MEDICAL RESEARCH 43.1(2015):67-79.
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