Differential effects of voluntary physical exercise on behavioral and brain-derived neurotrophic factor expression deficits in huntington’s disease transgenic mice

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 t...

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Bibliographic Details
Published in:	Neuroscience Vol. 141; no. 2; pp. 569 - 584
Main Authors:	Pang, T.Y.C., Stam, N.C., Nithianantharajah, J., Howard, M.L., Hannan, A.J.
Format:	Journal Article
Language:	English
Published:	Oxford Elsevier Ltd 01-01-2006 Elsevier
Subjects:	Age Factors Analysis of Variance Animals BDNF Behavior, Animal Biological and medical sciences Brain-Derived Neurotrophic Factor - deficiency Brain-Derived Neurotrophic Factor - genetics Corpus Striatum - metabolism Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases dementia Disease Models, Animal exercise Exploratory Behavior - physiology Frontal Lobe - metabolism Fundamental and applied biological sciences. Psychology Gene Expression Regulation - genetics gene-environment interactions Huntingtin Protein Huntington Disease - genetics Huntington Disease - metabolism Huntington Disease - physiopathology Huntington Disease - rehabilitation Male Maze Learning - physiology Medical sciences Mice Mice, Transgenic Nerve Tissue Proteins - genetics neurodegeneration Neurology Nuclear Proteins - genetics Physical Conditioning, Animal - methods Psychomotor Performance - physiology Reaction Time - genetics Reverse Transcriptase Polymerase Chain Reaction - methods RNA, Messenger - metabolism Running - physiology Time Factors Vertebrates: nervous system and sense organs wheel running wheel running BDNF gene-environment interactions SH neurodegeneration exercise dementia HD GAPDH WT ELISA Physical exercise Nervous system diseases Rodentia Huntington disease Transgenic animal Cerebral disorder Genetic disease Vertebrata Mammalia Mouse Central nervous system disease Degenerative disease Degeneration Behavior Brain derived neurotrophic factor Extrapyramidal syndrome
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0306-4522 1873-7544
DOI:	10.1016/j.neuroscience.2006.04.013