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

Research output: Contribution to journalArticle

50 Citations (Scopus)

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

Fingerprint

Denervation
N-Methyl-D-Aspartate Receptors
Amyloid
Nitric Oxide Synthase
Cerebral Cortex
Cholinergic Agents
Nitric Oxide Synthase Type I
Cholinergic Neurons
Polyamines
Calmodulin
Neurons
Wounds and Injuries

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

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

In: Brain Research Bulletin, Vol. 45, No. 4, 01.03.1998, p. 405-411.

Research output: Contribution to journalArticle

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. / β-amyloid-induced cholinergic denervation correlates with enhanced nitric oxide synthase activity in rat cerebral cortex : Reversal by NMDA receptor blockade. In: Brain Research Bulletin. 1998 ; Vol. 45, No. 4. pp. 405-411.
@article{fada2329ca0e4056afe46ffe9d487149,
title = "β-amyloid-induced cholinergic denervation correlates with enhanced nitric oxide synthase activity in rat cerebral cortex: Reversal by NMDA receptor blockade",
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.",
keywords = "β-amyloid, Cholinergic system, Ifenprodil tartrate, Magnocellular basal nucleus, N-methyl-D-aspartate receptor, Nitric Oxide synthase",
author = "S. O'Mahony and T. Harkany and Rensink, {A. A M} and I. {\'A}brah{\'a}m and {De Jong}, {G. I.} and Varga, {J. L.} and M. Zar{\'a}ndi and B. Penke and C. Nyakas and Luiten, {P. G M} and Leonard, {B. E.}",
year = "1998",
month = "3",
day = "1",
doi = "10.1016/S0361-9230(97)00405-X",
language = "English",
volume = "45",
pages = "405--411",
journal = "Brain Research Bulletin",
issn = "0361-9230",
publisher = "Elsevier Inc.",
number = "4",

}

TY - JOUR

T1 - β-amyloid-induced cholinergic denervation correlates with enhanced nitric oxide synthase activity in rat cerebral cortex

T2 - Reversal by NMDA receptor blockade

AU - O'Mahony, S.

AU - Harkany, T.

AU - Rensink, A. A M

AU - Ábrahám, I.

AU - De Jong, G. I.

AU - Varga, J. L.

AU - Zarándi, M.

AU - Penke, B.

AU - Nyakas, C.

AU - Luiten, P. G M

AU - Leonard, B. E.

PY - 1998/3/1

Y1 - 1998/3/1

N2 - 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.

AB - 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.

KW - β-amyloid

KW - Cholinergic system

KW - Ifenprodil tartrate

KW - Magnocellular basal nucleus

KW - N-methyl-D-aspartate receptor

KW - Nitric Oxide synthase

UR - http://www.scopus.com/inward/record.url?scp=0032031810&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032031810&partnerID=8YFLogxK

U2 - 10.1016/S0361-9230(97)00405-X

DO - 10.1016/S0361-9230(97)00405-X

M3 - Article

VL - 45

SP - 405

EP - 411

JO - Brain Research Bulletin

JF - Brain Research Bulletin

SN - 0361-9230

IS - 4

ER -