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| Status |
Public on Jun 01, 2004 |
| Title |
Triple treatment R6/2 mice |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Huntington’s disease is a genetic disease caused by a single mutation. It is characterised by progressive movement, emotional and cognitive deficits. R6/2 transgenic mice carrying the Huntington’s disease mutation have a progressive neurological phenotype, including deterioration in cognitive function. The mechanism underlying the cognitive deficits in R6/2 mice is unknown, but dysregulated gene expression, reduced neurotransmitter levels and abnormal synaptic function are present before the cognitive decline becomes pronounced. Our goal here was to ameliorate the cognitive phenotype in R6/2 mice using a combination drug therapy (tacrine, moclobemide and creatine) aimed boosting neurotransmitter levels in the brain. Treatment from 5 weeks of age prevented deterioration in two different cognitive tasks until at least 12 weeks. However, motor deterioration continued unabated. Microarray analysis of global gene expression revealed that many genes significantly up- or down-regulated in untreated R6/2 mice had returned towards normal levels after treatment. Thus dysregulated gene expression was reversed by the combination treatment in the R6/2 mice and probably underlies the observed improvements in cognitive function. Our study shows that cognitive decline caused by a genetic mutation can be slowed by a combination drug treatment, and gives hope that cognitive symptoms in HD can be treated.
Keywords = HD
Keywords = Huntingtin
Keywords = cognitive disorder
Keywords = R6/2
Keywords = transgenic mice
Keywords = gene expression
Keywords = microarray
Keywords: ordered
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| Contributor(s) |
Morton AJ, Hunt MJ, Hodges AK, Lewis PD, Dunnett SB, Jones L |
| Citation(s) |
15787692 |
| |
| Submission date |
Dec 08, 2003 |
| Last update date |
Feb 18, 2018 |
| Contact name |
Lesley Jones, Angela Hodges |
| E-mail(s) |
[email protected], [email protected]
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| Phone |
+44 2920 745175
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| Organization name |
Cardiff University School of Medicine
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| Department |
Psychological Medicine
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| Street address |
Heath Park
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| City |
Cardiff |
| ZIP/Postal code |
CF14 4XN |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL81 |
[MG_U74Av2] Affymetrix Murine Genome U74A Version 2 Array |
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| Samples (13)
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| Relations |
| BioProject |
PRJNA87871 |
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