BEHAVIOURAL PHENOTYPES RESCUED IN TAU KNOCK-OUT MICE BY RE-EXPRESSION OF A HUMAN TAU TRANSGENE

ANA DAMIANICH; SONIA ESPINDOLA; MARIA ELENA AVALE

Congreso; 9th World CongressIBRO2015; 2015

International Brain Research Organization

Tau is a microtubule-associated protein predominantly expressed in neurons and involved in many processes, such as microtubule polymerization and stabilization, neurite outgrowth and axonal transport. However, the essential role of Tau in the adult brain has been under debate during the last decade. Based on evidence demonstrating that neither gross behavioural nor neurochemical dysfunctions were observed in TauKO mice, Tau reduction has been proposed as a treatment strategy for tauopathies. However, some recent reports suggest that the lack of Tau might be detrimental in the adult brain, because TauKO mice show mild impairment in fine motor coordination or cognitive tasks. The aims of this work are to further evaluate the functional role of Tau in motor and cognitive tasks, comparing middle-aged wild type and TauKO mice; and to analyze if the expression of human Tau in the TauKO background leads to any phenotypic rescueWild-Type, TauKO and Htau mice were analyzed in the open field and the rotarod to assess spontaneous locomotion and motor coordination. Cognitive performance was also tested in the novel object recognition (NOR) task and the Morris Water Maze. In addition immunohistochemical analyses were done to analyze dopaminergic neurons in the SNpc of the three groups and quantified by stereology. Together, our results suggest that lack of Tau has an effect over motor and cognitive behaviours, and that re-expression of Tau with a full lenght human Tau transgene might rescue motor phenotypes but not cognitive deficits.