Resumo

The accumulation of amyloid-beta (A&Beta) peptides in the brain of human and rodents has been associated with the activation of glial cells, neuroinflammatory and oxidative responses, and cognitive deficits. These oxidative changes leave glutamate transporters more vulnerable and may result in reduction of their functions, resulting in excitotoxic damage. Herein, we evaluated the effects of atorvastatin, a HMG-CoA reductase inhibitor, in molecular and behavioral alterations induced by a single intracerebroventricular injection of aggregated A&Beta1-40 (400 pmol) in mice. An increased glial fibrilar acidic protein (GFAP) expression and cyclooxygenase-2 (COX-2) levels were observed by immunohistochemical analysis. Biochemical evaluation revealed an increased lipid peroxidation and impairment in the glutathione antioxidant system. Neuronal degeneration, as measured by Fluoro Jade labeling and propidium iodide incorporation, was found in the hippocampus of A&Beta1-40-treated mice. A&Beta1-40 also induced a marked decrease in glutamatergic transporters (GLAST and GLT-1) expression and in L-[3H] glutamate uptake in mice hippocampus, in addition to spatial learning and memory deficits evaluated in the Morris water maze task. Atorvastatin (10 mg/kg/day v.o.) was administered after A&Beta1-40 injection and through 7 consecutive days. Atorvastatin treatment was neuroprotective against cell degeneration induced by A&Beta1-40, reducing inflammatory and oxidative responses and increasing the expression of glutamatergic transporters. On the other hand, atorvastatin did not reverse the cognitive impairments and failed to alter the hippocampal glutamate uptake in A&Beta1-40¡Vtreated mice. These results reinforce and extend the notion of the potential neuroprotective action of atorvastatin against the neuronal toxicity induced by A&Beta1-40. In addition, the present findings suggest that the spatial learning and memory deficits induced by AƒÒ peptides in rodents may not be entirely related to neuronal damage.