RGD Reference Report - Wheel running and environmental enrichment differentially modify exon-specific BDNF expression in the hippocampus of wild-type and pre-motor symptomatic male and female Huntington's disease mice. - Rat Genome Database

RGD Reference Report - Wheel running and environmental enrichment differentially modify exon-specific BDNF expression in the hippocampus of wild-type and pre-motor symptomatic male and female Huntington's disease mice. - Rat Genome Database

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Wheel running and environmental enrichment differentially modify exon-specific BDNF expression in the hippocampus of wild-type and pre-motor symptomatic male and female Huntington's disease mice.
Authors:	Zajac, MS Pang, TY Wong, N Weinrich, B Leang, LS Craig, JM Saffery, R Hannan, AJ
Citation:	Zajac MS, etal., Hippocampus. 2010 May;20(5):621-36. doi: 10.1002/hipo.20658.
RGD ID:	10059353
Pubmed:	PMID:19499586 (View Abstract at PubMed)
DOI:	DOI:10.1002/hipo.20658 (Journal Full-text)
Brain-derived neurotrophic factor (BDNF) is an essential neurotrophin and regulation of its expression is complex due to multiple 5' untranslated exons which are separately spliced to a common coding exon to form unique mRNA transcripts. Disruption of BDNF gene expression is a key to the development of symptoms in Huntington's disease (HD), a fatal neurodegenerative condition. Abnormal epigenetic modifications are associated with reduced gene expression in late-stage HD but such regulation of BDNF gene expression has yet to be investigated. We hypothesized that BDNF gene expression is altered in the HD hippocampus of pre-motor symptomatic R6/1 transgenic HD mice, correlating with a change in the DNA methylation profile. The effects of wheel-running and environmental enrichment on wild-type mice, in association with a proposed environment-mediated correction of BDNF gene expression deficits in HD mice, were also investigated. Using real-time PCR, levels of total BDNF mRNA were found to be reduced in the hippocampus of both male and female HD mice. Wheel-running significantly increased total BDNF gene expression in all groups of mice except male HD mice. In contrast, environmental enrichment significantly increased expression only in male wild-type animals. Further quantification of BDNF exon-specific transcripts revealed sex-specific changes in relation to the effect of the HD mutation and differential effects on gene expression by wheel-running and environmental enrichment. The HD-associated reduction of BDNF gene expression was not due to increased methylation of the gene sequence. Furthermore, environment-induced changes in BDNF gene expression in the wild-type hippocampus were independent of the extent of DNA methylation. Overall, the results of this study provide new insight into the role of BDNF in HD pathogenesis in addition to the mechanisms regulating normal BDNF gene expression.

Only show annotations with direct experimental evidence (0 objects hidden)

Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
BDNF	Human	Huntington's disease		ISO	Bdnf (Mus musculus)		RGD
Bdnf	Rat	Huntington's disease		ISO	Bdnf (Mus musculus)		RGD
Bdnf	Mouse	Huntington's disease		IEP			RGD

Genes (Rattus norvegicus)


Bdnf (brain-derived neurotrophic factor)

Genes (Mus musculus)


Bdnf (brain derived neurotrophic factor)

Genes (Homo sapiens)


BDNF (brain derived neurotrophic factor)