N-methyl-D-aspartate receptor antagonist MK-801 and radical scavengers protect cholinergic nucleus basalis neurons against β-amyloid neurotoxicity

T. Harkany, J. Mulder, M. Sasvári, I. Ábrahám, C. Kónya, M. Zarándi, B. Penke, P. G.M. Luiten, C. Nyakas

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

Previous experimental data indicate the involvement of Ca2+-related excitotoxic processes, possibly mediated by N-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 the magnocellular nucleus basalis of rats, while neuroprotection was achieved by either single or combined administration 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 the nucleus basalis elicited 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 the single drug administrations protected against the neurotoxic events, whereas the combined treatment failed to ameliorate βA toxicity.

Original languageEnglish
Pages (from-to)109-121
Number of pages13
JournalNeurobiology of Disease
Volume6
Issue number2
DOIs
Publication statusPublished - Apr 1999

Keywords

  • Cholinergic system
  • N-methyl-D-aspartate receptor
  • Neuroprotection
  • Vitamin
  • β-amyloid

ASJC Scopus subject areas

  • Neurology

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