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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2008-8-18
pubmed:abstractText
Conditional double knockout of presenilin-1 and presenilin-2 (cDKO) in forebrain of mice led to brain atrophy, tau hyperphosphorylation, synaptic dysfunction and cognitive deficit. These brain changes recapitulated most of the neurodegenerative phenotypes of Alzheimer's disease (AD). In this report, we have investigated the effects of 4-month calorie restriction (CR) regimen on different phenotypes in cDKO mice. We found that CR improved novel object recognition and contextual fear conditioning memory in the cDKO mice. Histological and biochemical analysis showed that CR attenuated ventricle enlargement, caspase-3 activation and astrogliosis. In addition, the induction of tau hyperphosphorylation in the cDKO mice was reduced by CR, possibly through reduction of p25 accumulation and aberrant CDK5 activation. Finally, DNA microarray analysis demonstrated that CR could increase the expression of neurogenesis related genes and decrease the expression of inflammation related genes in the hippocampus of cDKO mice. The possible molecular mechanisms of the CR effects on alleviating AD pathogenesis have been discussed.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1558-1497
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
29
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1502-11
pubmed:meshHeading
pubmed-meshheading:17499883-Animals, pubmed-meshheading:17499883-Avoidance Learning, pubmed-meshheading:17499883-Caloric Restriction, pubmed-meshheading:17499883-Caspase 3, pubmed-meshheading:17499883-Cell Death, pubmed-meshheading:17499883-Cell Proliferation, pubmed-meshheading:17499883-Cognition Disorders, pubmed-meshheading:17499883-Disease Models, Animal, pubmed-meshheading:17499883-Encephalitis, pubmed-meshheading:17499883-Female, pubmed-meshheading:17499883-Gene Expression Regulation, pubmed-meshheading:17499883-Gliosis, pubmed-meshheading:17499883-Hippocampus, pubmed-meshheading:17499883-Male, pubmed-meshheading:17499883-Memory Disorders, pubmed-meshheading:17499883-Mice, pubmed-meshheading:17499883-Mice, Knockout, pubmed-meshheading:17499883-Neurodegenerative Diseases, pubmed-meshheading:17499883-Phenotype, pubmed-meshheading:17499883-Presenilin-1, pubmed-meshheading:17499883-Presenilin-2, pubmed-meshheading:17499883-Prosencephalon, pubmed-meshheading:17499883-tau Proteins
pubmed:year
2008
pubmed:articleTitle
Calorie restriction ameliorates neurodegenerative phenotypes in forebrain-specific presenilin-1 and presenilin-2 double knockout mice.
pubmed:affiliation
Shanghai Institute of Brain Functional Genomics, MOE & STCSM Key Lab of Brain Functional Genomics, East China Normal University, Shanghai 200062, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't