Document Detail


Differential effects of voluntary physical exercise on behavioral and brain-derived neurotrophic factor expression deficits in Huntington's disease transgenic mice.
MedLine Citation:
PMID:  16716524     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Huntington's disease is a fatal neurodegenerative disorder caused by a mutation of the huntingtin gene and involves progressive motor abnormalities (including chorea), cognitive deficits (dementia) as well as psychiatric symptoms. We have previously demonstrated that environmental enrichment slows the onset and progression of Huntington's disease in transgenic mice. Here, we investigated the effects of enhanced physical exercise on disease progression and brain-derived neurotrophic factor expression. Standard-housed Huntington's disease mice developed phenotypic rear-paw clasping by 16 weeks of age, displayed abnormal rearing behavior, deficits in motor co-ordination and of spatial working memory. Huntington's disease mice with access to running wheels exhibited delayed onset of rear-paw clasping, normalized levels of rearing behavior and amelioration of the cognitive deficits. However, in contrast to our previous environmental enrichment studies, there was no rescue of motor coordination deficits in wheel-running Huntington's disease mice. An abnormal accumulation of brain-derived neurotrophic factor protein in the frontal cortex of Huntington's disease mice was unaffected by running. Striatal and hippocampal brain-derived neurotrophic factor protein levels were unchanged. Brain-derived neurotrophic factor mRNA levels were reduced in the anterior cortex, striatum and hippocampus of Huntington's disease mice, and only striatal deficits were ameliorated by running. Overall, we show that voluntary physical exercise delays the onset of Huntington's disease and the decline in cognitive ability. In addition, our results reveal that some aspects of hippocampal dependent memory are not entirely reliant on sustained hippocampal brain-derived neurotrophic factor expression.
Authors:
T Y C Pang; N C Stam; J Nithianantharajah; M L Howard; A J Hannan
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-05-22
Journal Detail:
Title:  Neuroscience     Volume:  141     ISSN:  0306-4522     ISO Abbreviation:  Neuroscience     Publication Date:  2006 Aug 
Date Detail:
Created Date:  2006-07-24     Completed Date:  2006-10-04     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7605074     Medline TA:  Neuroscience     Country:  United States    
Other Details:
Languages:  eng     Pagination:  569-84     Citation Subset:  IM    
Affiliation:
Howard Florey Institute, University of Melbourne, Parkville, Victoria 3010, Australia. t.pang@hfi.unimelb.edu.au
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MeSH Terms
Descriptor/Qualifier:
Age Factors
Analysis of Variance
Animals
Behavior, Animal
Brain-Derived Neurotrophic Factor / deficiency*,  genetics
Corpus Striatum / metabolism
Disease Models, Animal
Exploratory Behavior / physiology
Frontal Lobe / metabolism
Gene Expression Regulation / genetics
Huntington Disease / genetics,  metabolism*,  physiopathology,  rehabilitation*
Male
Maze Learning / physiology
Mice
Mice, Transgenic
Nerve Tissue Proteins / genetics
Nuclear Proteins / genetics
Physical Conditioning, Animal / methods*
Psychomotor Performance / physiology
RNA, Messenger / metabolism
Reaction Time / genetics
Reverse Transcriptase Polymerase Chain Reaction / methods
Running / physiology
Time Factors
Chemical
Reg. No./Substance:
0/Brain-Derived Neurotrophic Factor; 0/Huntington protein, mouse; 0/Nerve Tissue Proteins; 0/Nuclear Proteins; 0/RNA, Messenger

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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