TitleEffects of diet on adenosine monophosphate-activated protein kinase activity and disease progression in an amyotrophic lateral sclerosis model
AuthorsZhao, Zichun
Sui, Yanling
Gao, Wenchao
Cai, Bin
Fan, Dongsheng
AffiliationPeking Univ, Hosp 3, Dept Neurol, Beijing 100191, Peoples R China.
Peking Univ, Hosp 3, Dept Neurol, 49 North Garden Rd, Beijing 100191, Peoples R China.
KeywordsAmyotrophic lateral sclerosis
metabolism
adenosine monophosphate-activated protein kinase
heat shock protein-70
calorie restriction
high-fat diet
LIFE-SPAN
NEURONAL SURVIVAL
MOUSE MODEL
MICE
ENERGY
AMPK
ALS
Issue Date2015
Publisherjournal of international medical research
CitationJOURNAL OF INTERNATIONAL MEDICAL RESEARCH.2015,43,(1),67-79.
AbstractObjectives 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.
URIhttp://hdl.handle.net/20.500.11897/309152
ISSN0300-0605
DOI10.1177/0300060514554725
IndexedSCI(E)
PubMed
Appears in Collections:第三医院

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