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Previous experimental data indicate the involvement of Ca2+-related excitotoxic processes, possibly mediated byN-Methyl-d-Aspartate (NMDA) receptors, in β-amyloid (βA) neurotoxicity. On the other hand, other lines of evidence support the view that free radical generation is a critical step in the βA-induced neurodegenerative cascade. In the present study, therefore, a neuroprotective strategy was applied to explore the contributions of each of these pathways in βA toxicity. βA(1–42)was injected into themagnocellular nucleus basalisof rats, while neuroprotection was achieved by eithersingleorcombinedadministration of the NMDA receptor antagonist MK-801 (2.5 mg/kg) and/or a vitamin E and C complex (150 mg/kg). The degree of neurodegeneration was determined by testing the animals in consecutive series of behavioral tasks, including elevated plus maze, passive avoidance learning, small open-field and open-field paradigms, followed by acetylcholinesterase (AChE), choline-acetyltransferase (ChAT), and superoxide dismutase (SOD) biochemistry. βA injected in thenucleus basaliselicited significant anxiety in the elevated plus maze, derangement of passive avoidance learning, and altered spontaneous behaviors in both open-field tasks. A significant decrease in both AChE and ChAT accompanied by a similar decrement of MnSOD, but not of Cu/ZnSOD provided neurochemical substrates for the behavioral changes. Each of thesingledrug administrations protected against the neurotoxic events, whereas thecombinedtreatment failed to ameliorate βA toxicity. |
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