Alterations on Na+,K+-ATPase and Acetylcholinesterase Activities Induced by Amyloid-β Peptide in Rat Brain and GM1 Ganglioside Neuroprotective Action

Alzheimer's disease (AD) is a neurodegenerative disorder whose pathogenesis involves production and aggregation of amyloid-beta peptide (A beta). A beta-induced toxicity is believed to involve alterations on as Na+,K+-ATPase and acetylcholinesterase (AChE) activities, prior to neuronal death. Drugs able to prevent or to reverse these biochemical changes promote neuroprotection. GM1 is a ganglioside proposed to have neuroprotective roles in AD models, through mechanisms not yet fully understood. Therefore, this study aimed to investigate the effect of A beta 1-42 infusion and GM1 treatment on recognition memory and on Na+,K+-ATPase and AChE activities, as well as, on antioxidant defense in the brain cortex and the hippocampus. For these purposes, Wistar rats received i.c.v. infusion of fibrilar A beta 1-42 (2 nmol) and/or GM1 (0.30 mg/kg). Behavioral and biochemical analyses were conducted 1 month after the infusion procedures. Our results showed that GM1 treatment prevented A beta-induced cognitive deficit, corroborating its neuroprotective function. A beta impaired Na+,K+-ATPase and increase AChE activities in hippocampus and cortex, respectively. GM1, in turn, has partially prevented A beta-induced alteration on Na+,K+-ATPase, though with no impact on AChE activity. A beta caused a decrease in antioxidant defense, specifically in hippocampus, an effect that was prevented by GM1 treatment. GM1, both in cortex and hippocampus, was able to increase antioxidant scavenge capacity. Our results suggest that A beta-triggered cognitive deficit involves region-specific alterations on Na+,K+-ATPase and AChE activities, and that GM1 neuroprotection involves modulation of Na+,K+-ATPase, maybe by its antioxidant properties. Although extrapolation from animal findings is difficult, it is conceivable that GM1 could play an important role in AD treatment.