IFIBIO HOUSSAY   25014
INSTITUTO DE FISIOLOGIA Y BIOFISICA BERNARDO HOUSSAY
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
LONG-TERM OVEREXPRESSION OF THE NEURODEGENERATIVE DISEASE-RELATED PROTEIN TDP-43 LEADS TO TIME-DEPENDENT BEHAVIORAL DECLINE IN TRANSGENIC MICE
Autor/es:
SILVA PR; ALFIERI JA; IGAZ LM
Lugar:
Buenos Aires
Reunión:
Congreso; XXX Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias (SAN); 2015
Institución organizadora:
Sociedad Argentina de Investigación en Neurociencias (SAN)
Resumen:
Frontotemporal Dementia (FTD) and amyotrophic lateral sclerosis (ALS) are two neurodegenerative diseases associated to mislocalization and aggregation of TAR DNA-binding protein 43 (TDP-43). To investigate the time course of this proteinopathy, we used as a model transgenic mice conditionally overexpressing human wild-type TDP 43 protein (hTDP-43-WT). We previously characterized and evaluated the behavioral phenotype (including motor, cognitive and social performance) 1-month after transgene induction, when mice display an impairment in cognitive and social domains in the absence of motor abnormalities. In the present study we analyzed the behavior of mice after long-term (12 months) transgene induction, performing a battery of tests to determine if the phenotypes worsen as the animals age. Our results reveal a decreased performance on the rotarod test and in the hanging wire test, indicating a motor phenotype that was absent in younger mice. In addition, long-term hTDP-43-WT expression led to hiperlocomotion in the open field test. Regarding the cognitive and social phenotypes established early on, they are still present in older mice, including altered social interaction and Y-maze tests. Our findings demonstrate a time-dependent emergence of a motor phenotype in older hTDP-43-WT transgenic mice, recapitulating aspects of clinical FTD presentations with motor involvement in human patients, and providing a complementary model for studying TDP-43 proteinopathies.