Estudo bioquímico e comportamental em camundongos submetidos à infusão intracerebroventricular dos peptídeos beta-amilóide AB1-40 E AB25-35 e o papel neuroprotetor da atorvastatina

Abstract

The accumulation and aggregation of beta-amyloid peptide (Aâ) in brain of patients with Alzheimer's disease results in activation of glial cells, which in turn may initiate inflammatory responses, release of inflammatory proteins and reactive oxygen species. These changes leave more vulnerable glutamatergic transporters and may result in reduction of their functions. In this study, the effects of intracerebroventricular infusion of peptides Aâ1-40 and Aâ25-35, on cognition, uptake of L-[3H] glutamate, oxidative stress, inflammation and cell death in mice were evaluated. The peptide Aâ1-40 appears to be more potent that the Aâ25-35, according to the methods studied, causing cell death and production of the inflammatory COX-2 protein. The infusion of both peptides Aâ1-40 and Aâ25-35 caused cognitive impairment, decreased uptake of L-[3H] glutamate and transporters GLAST and GLT-1, increased lipid peroxidation and reduction in NPSH and activation of glial cells. In order to seek neuroprotective approaches, atorvastatin, an inhibitor of HMG-CoA reductase, was administered for 7 days in animals that received infusion of peptides Aâ1-40 or Aâ25-35. Treatment with atorvastatin (10 mg/Kg/day) was not able to reverse the cognitive decline and decreased uptake of glutamate, but was neuroprotective against cell death by increasing the expression of glutamatergic transporters, decreasing inflammatory mediators and TBARS. Thus, atorvastatin has a potential neuroprotective effect against toxicity induced by beta-amyloid peptides.