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http://hdl.handle.net/2445/183388
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DC Field | Value | Language |
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dc.contributor.author | Giralt Torroella, Albert | - |
dc.contributor.author | Puigdellívol Cañadell, Maria del Mar | - |
dc.contributor.author | Carreton, Olga | - |
dc.contributor.author | Paoletti Rubia, Paola | - |
dc.contributor.author | Valero, J. | - |
dc.contributor.author | Parra-Damas, A. | - |
dc.contributor.author | Saura Antolín, Carlos A. (Carlos Alberto) | - |
dc.contributor.author | Alberch i Vié, Jordi, 1959- | - |
dc.contributor.author | Ginés Padrós, Silvia | - |
dc.date.accessioned | 2022-02-21T18:14:32Z | - |
dc.date.available | 2022-02-21T18:14:32Z | - |
dc.date.issued | 2012-03-15 | - |
dc.identifier.issn | 0964-6906 | - |
dc.identifier.uri | http://hdl.handle.net/2445/183388 | - |
dc.description.abstract | Huntington's disease (HD) is an autosomal dominant progressive neurodegenerative disorder caused by an expanded CAG/polyglutamine repeat in the coding region of the huntingtin (htt) gene. Although HD is classically considered a motor disorder, there is now considerable evidence that early cognitive deficits appear in patients before the onset of motor disturbances. Here we demonstrate early impairment of long-term spatial and recognition memory in heterozygous HD knock-in mutant mice (Hdh(Q7/Q111)), a genetically accurate HD mouse model. Cognitive deficits are associated with reduced hippocampal expression of CREB-binding protein (CBP) and diminished levels of histone H3 acetylation. In agreement with reduced CBP, the expression of CREB/CBP target genes related to memory, such c-fos, Arc and Nr4a2, was significantly reduced in the hippocampus of Hdh(Q7/Q111) mice compared with wild-type mice. Finally, and consistent with a role of CBP in cognitive impairment in Hdh(Q7/Q111) mice, administration of the histone deacetylase inhibitor trichostatin A rescues recognition memory deficits and transcription of selective CREB/CBP target genes in Hdh(Q7/Q111) mice. These findings demonstrate an important role for CBP in cognitive dysfunction in HD and suggest the use of histone deacetylase inhibitors as a novel therapeutic strategy for the treatment of memory deficits in this disease. | - |
dc.format.extent | 14 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Oxford University Press | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.1093/hmg/ddr552 | - |
dc.relation.ispartof | Human Molecular Genetics, 2012, vol. 21, num. 6, p. 1203-1216 | - |
dc.relation.uri | https://doi.org/10.1093/hmg/ddr552 | - |
dc.rights | (c) Giralt Torroella, Albert et al., 2012 | - |
dc.source | Articles publicats en revistes (Biomedicina) | - |
dc.subject.classification | Corea de Huntington | - |
dc.subject.classification | Models animals en la investigació | - |
dc.subject.other | Huntington's chorea | - |
dc.subject.other | Animal models in research | - |
dc.title | Long-term memory deficits in Huntington's disease are associated with reduced CBP histone acetylase activity | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 694139 | - |
dc.date.updated | 2022-02-21T18:14:33Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
Appears in Collections: | Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) Articles publicats en revistes (Biomedicina) |
Files in This Item:
File | Description | Size | Format | |
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694139.pdf | 605.59 kB | Adobe PDF | View/Open |
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