Role of cannabinoid system on tau activity and its relation to the cognitive performance in a model of sporadic Alzheimer's Disease in rats

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive impairment, increase of fear- and anxiety-related behaviors and reaction time in attention tasks and importantly, a marked deficit of spatial and operational memory. AD is also known by neurofibrilar tangles, generated by hyperphosphorylated tau protein accumulation. Studies showed that cannabinoid drugs interfered with tau pathway and that anandamide (ANA, an endogenous cannabinoid) is related to the cognitive deficits associated to AD. However, it is remain unknown the relations between ANA and tau degradation, as well as the role of chaperones BAG2/Hsp70 (molecules also involved in tau degradation) in this system. It is also unclear the effect of exogenous ANA on cognitive performance in an animal model of AD. Thus, the objective of this study is to evaluate the action of ANA on tau activity in a model of DA and its relationship to the cognitive performance. Using a model of intracerebroventricular administration of streptozotocin and after receive ANA chronically, animals will be submitted to cognitive and molecular tests. Memory and attention processes will be evaluated by classic fear conditioning, object recognition and pre-pulse inhibition. ANA effects on phosphorylated and total tau, Hsp70 and BAG2 expression and levels will be analyzed with PCR and Western Blotting techniques. (AU)