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Title: Long-term memory deficits in Huntington's disease are associated with reduced CBP histone acetylase activity
Author: Giralt Torroella, Albert
Puigdellívol Cañadell, Maria del Mar
Carreton, Olga
Paoletti Rubia, Paola
Valero, J.
Parra-Damas, A.
Saura Antolín, Carlos A. (Carlos Alberto)
Alberch i Vié, Jordi
Ginés Padrós, Silvia
Keywords: Corea de Huntington
Models animals en la investigació
Huntington's chorea
Animal models in research
Issue Date: 15-Mar-2012
Publisher: Oxford University Press
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.
Note: Reproducció del document publicat a:
It is part of: Human Molecular Genetics, 2012, vol. 21, num. 6, p. 1203-1216
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ISSN: 0964-6906
Appears in Collections:Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Biomedicina)

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