EVALUATION OF BEHAVIORAL PHENOTYPES BEFORE AND AFTER TRANSGENE SUPPRESSION IN A CONDITIONAL TDP-43 MOUSE MODEL OF FRONTOTEMPORAL DEMENTIA /AMYOTROPHIC LATERAL SCLEROSIS.

NIEVA GV; SILVA PR; IGAZ LM

Buenos Aires

Simposio; AAIC (Alzheimer´s Association International Conference) Satellite Symposium, ?Discover New Pathways in Alzheimer's and Dementia Research in Latin America.; 2018

Alzheimer´s Association

Mislocalizationand aggregation of TDP-43 are two common features of frontotemporal dementia(FTD) as well as amyotrophic lateral sclerosis (ALS). We developed transgenicmice conditionally overexpressing human wild-type TDP-43 protein (hTDP-43- WT)in forebrain neurons, a model that recapitulate key features of FTD/ALS.  Afterpost-weaning transgene (TG) induction during 1 month, these mice display anearly behavioral phenotype, including impaired cognitive and social function withno substantial motor abnormalities. In this study we evaluated the behavior beforeand after 2 weeks of TG suppression. hTDP-43-WTmice evaluated in the Y-maze test displayed normal spatial and working memoryboth before and after the suppression protocol. This indicates that TGsuppression prevents the installment of early cognitive deficits. TGsuppression also prevented the development of the mild spasticity observed inmice expressing the TG for 1 month. Both locomotion and exploratory behavior(open field test) and motor coordination (rotarod test) were indistinguishablefrom controls before and after TG suppression. Since the results of these testswere consistent with the ones seen after 1 month of TG expression, thesuppression protocol had no unspecific effects on motor behavior. No socialdeficits were found before TG suppresion. These results contribute to ourunderstanding of FTD/ALS and provide valuable information for susceptibilitywindows in therapeutic strategies.