β-amyloid-induced cholinergic denervation correlates with enhanced nitric oxide synthase activity in rat cerebral cortex: Reversal by NMDA receptor blockade

S. O'Mahony, T. Harkany, A. A.M. Rensink, I. Ábrahám, G. I. De Jong, J. L. Varga, M. Zarándi, B. Penke, C. Nyakas, P. G.M. Luiten, B. E. Leonard

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Abstract

Ample experimental evidence indicates that acute β-amyloid infusion into the nucleus basalis of rats elicits abrupt degeneration of the magnocellular cholinergic neurons projecting to the cerebral cortex. In fact, involvement of a permanent Ca2+ overload, partially via N-methyl-D- aspartate (NMDA) receptors, was proposed as a pivotal mechanism in β- amyloidinduced neurodegeneration. A definite measure of NMDA receptor- mediated processes and subsequent Ca2+ entry is the induction of Ca2+/calmodulin-activated neuronal nitric oxide synthase (nNOS) in nerve cells. In the present account we therefore assessed activation of nNOS in correlation with cholinergic decline after β-amyloid(1-42) or β-amyloid(25- 35) infusion into the rat nucleus basalis. The results demonstrate the β- amyloid conformation-dependent enhancement of cortical nitric oxide synthase (NOS) activity. Furthermore, chronic application of the polyamine site NMDA receptor blocker ifenprodil effectively attenuated β-amyloid neurotoxicity. We propose that nNOS activation reflects the degree of β-amyloid-induced excitotoxic injury in a proportional manner. Moreover, Ca2+-mediated processes via NMDA receptors, or direct binding of β-amyloid to this receptor may be a critical step in the neurotoxic mechanisms in vivo.

Original languageEnglish
Pages (from-to)405-411
Number of pages7
JournalBrain Research Bulletin
Volume45
Issue number4
DOIs
Publication statusPublished - Mar 1 1998

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Keywords

  • Cholinergic system
  • Ifenprodil tartrate
  • Magnocellular basal nucleus
  • N-methyl-D-aspartate receptor
  • Nitric Oxide synthase
  • β-amyloid

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

O'Mahony, S., Harkany, T., Rensink, A. A. M., Ábrahám, I., De Jong, G. I., Varga, J. L., Zarándi, M., Penke, B., Nyakas, C., Luiten, P. G. M., & Leonard, B. E. (1998). β-amyloid-induced cholinergic denervation correlates with enhanced nitric oxide synthase activity in rat cerebral cortex: Reversal by NMDA receptor blockade. Brain Research Bulletin, 45(4), 405-411. https://doi.org/10.1016/S0361-9230(97)00405-X