IFIBIO HOUSSAY   25014
INSTITUTO DE FISIOLOGIA Y BIOFISICA BERNARDO HOUSSAY
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
CONDITIONAL MOUSE MODELS OF TDP-43 PROTEINOPATHIES.
Autor/es:
IGAZ LM
Lugar:
Buenos Aires
Reunión:
Congreso; 2nd FALAN (Federation of Latin American and Caribbean Neurosciences) Congress; 2016
Institución organizadora:
FALAN (Federation of Latin American and Caribbean Neurosciences)
Resumen:
TDP-43 mislocalization and aggregation are hallmark features of amyotrophiclateral sclerosis and frontotemporal dementia (FTD). We have previously shownin mice that inducible overexpression of a cytoplasmically-localized form ofTDP-43 (TDP-43-ΔNLS) in forebrain neurons evokes neuropathological changes thatrecapitulate several features of TDP-43 proteinopathies. In the present study,we performed a battery of behavioral tests to evaluate motor, cognitive andsocial phenotypes in this model. We found that transgene (Tg) induction bydoxycycline removal at weaning led to motor abnormalities including hyperlocomotion,increased spasticity and impaired coordination and balance. Cognitiveassessment demonstrated impaired recognition and spatial memory. Remarkably,TDP-43-ΔNLS mice displayed deficits in social behavior, mimicking a key aspectof FTD. In order to analyze if these symptoms were reversible, we suppressed Tgexpression for 14 d in young mice, which showed an established behavioralphenotype but modest neurodegeneration, and found that motor and cognitivedeficits were ameliorated; however, social performance remained altered. Inolder mice exhibiting overt neurodegeneration, the motoric phenotypes were notreversible. These results indicate that TDP-43-ΔNLS mice display several corebehavioral features of FTD with motor neuron disease and might serve as avaluable tool to unveil the underlying mechanisms of this and other TDP-43proteinopathies.