Giralt Torroella, AlbertPuigdellívol Cañadell, Maria del MarCarreton, OlgaPaoletti Rubia, PaolaValero, J.Parra-Damas, A.Saura Antolín, Carlos A. (Carlos Alberto)Alberch i Vié, Jordi, 1959-Ginés Padrós, Silvia2022-02-212022-02-212012-03-150964-6906https://hdl.handle.net/2445/183388Huntington'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.14 p.application/pdfeng(c) Giralt Torroella, Albert et al., 2012Corea de HuntingtonModels animals en la investigacióHuntington's choreaAnimal models in researchinfo:eu-repo/semantics/article6941392022-02-21info:eu-repo/semantics/openAccess