IFIBIO HOUSSAY   25014
INSTITUTO DE FISIOLOGIA Y BIOFISICA BERNARDO HOUSSAY
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
CONDITIONAL OVEREXPRESSION OF THE NEURODEGENERATIVE DISEASE-RELATED PROTEIN TDP-43 LEADS TO COGNITIVE AND SOCIAL ABNORMALITIES IN TRANSGENIC MICE
Autor/es:
ALFIERI JA; IGAZ LM
Lugar:
Huerta Grande, Cordoba, Argenitna
Reunión:
Congreso; XXIX Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias (SAN); 2014
Institución organizadora:
Sociedad Argentina de Investigación en Neurociencias (SAN)
Resumen:
TDP-43 mislocalization and aggregation are hallmark features of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), diseases known as ?TDP-43 proteinopathies?. We have previously shown in mice that inducible overexpression of human wild-type TDP-43 protein (hTDP-43-WT) or a cytoplasmically localized form (hTDP-43-NLS) in forebrain neurons evokes neuropathological changes that recapitulate several features of TDP-43 proteinopathies. Moreover, detailed behavioral phenotyping demonstrated that TDP-43-NLS mice present motor, cognitive and social abnormalities displaying several core behavioral features of FTD. In the present study, we performed a variety of tests to evaluate the effect of hTDP-43-WT expression on behavioral phenotype. Our results indicate that young hTDP-43-WT transgenic mice, in opposition to TDP-43-NLS mice, present a normal motor phenotype compared to control littermates, as assessed by rotarod performance, spontaneous locomotor ac tivity in the open field test and a milder degree of spasticity shown by a clasping phenotype. We are currently performing a broader behavioral characterization and these studies suggests an impairment in cognitive and social domains in the absence of overt motor abnormalities, providing further validation for its usage as a model for FTD. The results from these studies will contribute to address in vivo the pathogenic mechanisms underlying TDP-43 proteinopathies.