Amb motiu del tancament d'estiu, la validació de documents es reprendrà a partir del 28 d'agost de 2026. Disculpeu les molèsties.
Con motivo del cierre de verano, la validación de documentos se reanudará a partir del 28 de agosto de 2026. Disculpad las molestias
Due to the summer closure, document validation will resume starting August 28, 2026. We apologize for any inconvenience.

Files

694139.pdf (605.59 KB)

Document type

Article

Version

Published version

Publication date

2012-03-15

All rights reserved

Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/183388

Long-term memory deficits in Huntington's disease are associated with reduced CBP histone acetylase activity

Journal Title

Authors

Director/Tutor

Journal ISSN

Volume Title

Related resource

https://doi.org/10.1093/hmg/ddr552

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.

Subject

Corea de Huntington, Models animals en la investigació

Subject (English)

Huntington's chorea, Animal models in research

Citation

Collections

Articles publicats en revistes (Biomedicina)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

Citation

GIRALT TORROELLA, Albert, et al. Long-term memory deficits in Huntington's disease are associated with reduced CBP histone acetylase activity. Human Molecular Genetics. 2012. Vol. 21, num. 6, pags. 1203-1216. ISSN 0964-6906. [consulted: 18 of August of 2026]. Available at: https://hdl.handle.net/2445/183388

Export metadata

JSON - METS

Share record