Striatal Projection Neurons Require Huntingtin for Synaptic Connectivity and Survival.
Cell Rep
; 30(3): 642-657.e6, 2020 01 21.
Article
em En
| MEDLINE
| ID: mdl-31968243
ABSTRACT
Huntington's disease (HD) is caused by an autosomal dominant polyglutamine expansion mutation of Huntingtin (HTT). HD patients suffer from progressive motor, cognitive, and psychiatric impairments, along with significant degeneration of the striatal projection neurons (SPNs) of the striatum. HD is widely accepted to be caused by a toxic gain-of-function of mutant HTT. However, whether loss of HTT function, because of dominant-negative effects of the mutant protein, plays a role in HD and whether HTT is required for SPN health and function are not known. Here, we delete Htt from specific subpopulations of SPNs using the Cre-Lox system and find that SPNs require HTT for motor regulation, synaptic development, cell health, and survival during aging. Our results suggest that loss of HTT function in SPNs could play a critical role in HD pathogenesis.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Sinapses
/
Corpo Estriado
/
Proteína Huntingtina
/
Rede Nervosa
/
Neurônios
Limite:
Animals
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article