|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|
|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|
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.
|资助机构||National Natural Sciences Foundation of China|
|作者单位||Peking Univ, Hosp 3, Dept Neurol, Beijing 100191, Peoples R China|
|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.|