Carregant...
Fitxers
Tipus de document
ArticleVersió
Versió publicadaData de publicació
Llicència de publicació
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/199962
Postnatal Foxp2 regulates early psychiatric-like phenotypes and associated molecular alterations in the R6/1 transgenic mouse model of Huntington's disease
Títol de la revista
Director/Tutor
ISSN de la revista
Títol del volum
Recurs relacionat
Resum
Huntington's Disease (HD) is a devastating disorder characterized by a triad of motor, psychiatric and cognitive manifestations. Psychiatric and emotional symptoms appear at early stages of the disease which are consistently described by patients and caregivers among the most disabling. Here, we show for the first time that Foxp2 is strongly associated with some psychiatric-like disturbances in the R6/1 mouse model of HD. First, 4-week-old (juvenile) R6/1 mice behavioral phenotype was characterized by an increased impulsive-like behavior and less aggressive-like behavior. In this line, we identified an early striatal downregulation of Foxp2 protein starting as soon as at postnatal day 15 that could explain such deficiencies. Interestingly, the rescue of striatal Foxp2 levels from postnatal stages completely reverted the impulsivity-phenotype and partially the social impairments concomitant with a rescue of dendritic spine pathology. A mass spectrometry study indicated that the rescue of spine loss was associated with an improvement of several altered proteins related with cytoskeleton dynamics. Finally, we reproduced and mimicked the impulsivity and social deficits in wild type mice by reducing their striatal Foxp2 expression from postnatal stages. Overall, these results imply that early postnatal reduction of Foxp2 might contribute to the appearance of some of the early psychiatric symptoms in HD.
Matèries (anglès)
Citació
Citació
RODRÍGUEZ URGELLÉS, Ened, RODRÍGUEZ NAVARRO, Irene, BALLASCH, Ivan, DEL TORO, Daniel, DEL CASTILLO, Ignacio, BRITO, Verónica, ALBERCH I VIÉ, Jordi, GIRALT TORROELLA, Albert. Postnatal Foxp2 regulates early psychiatric-like phenotypes and associated molecular alterations in the R6/1 transgenic mouse model of Huntington's disease. _Neurobiology of Disease_. 2022. Vol. 173, núm. 105854. [consulta: 28 de gener de 2026]. ISSN: 0969-9961. [Disponible a: https://hdl.handle.net/2445/199962]