Nitric oxide stimulates cGMP formation in rat optic nerve axons, providing a specific marker of axon viability

Nitric oxide stimulates cGMP formation in rat optic nerve axons, providing a specific marker of... A major transduction pathway for nitric oxide (NO) is stimulation of soluble guanylyl cyclase and the generation of cyclic GMP (cGMP). In the central nervous system, the NO–cGMP pathway has previously been associated primarily with synapses, particularly glutamatergic synapses. We report here that NO caused a large increase in the levels of cGMP in a central white matter tract devoid of synapses, namely in the rat isolated optic nerve. Cyclic GMP immunohistochemistry indicated that this response was confined to the axons. Accordingly, nerves previously subjected to 1 h of oxygen/glucose deprivation, which leads to irreversible axonal damage, displayed an 80% reduction in their subsequent capacity to generate cGMP in response to NO and a corresponding reduction in the numbers of cGMP‐immunostained axons. Protection of the axon cGMP response against this insult was achieved by omission of Ca2 + or Na + from the incubation medium, and by the pharmacological agents tetrodotoxin, lamotrigine, BW619C89 and BW1003C87, all of which protect axonal structure from oxygen/glucose deprivation‐induced damage. The results suggest that the NO–cGMP pathway has a hitherto unsuspected function in the optic nerve. Additionally, the expression of NO‐stimulated guanylyl cyclase in optic nerve axons provides a simple, sensitive and specific marker of their functional integrity that is likely to be valuable in investigating the mechanisms responsible for axon degeneration in ischaemia and other conditions. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Journal of Neuroscience Wiley

Nitric oxide stimulates cGMP formation in rat optic nerve axons, providing a specific marker of axon viability

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Publisher
Wiley
Copyright
Copyright © 1999 Wiley Subscription Services, Inc., A Wiley Company
ISSN
0953-816X
eISSN
1460-9568
D.O.I.
10.1046/j.1460-9568.1999.00874.x
Publisher site
See Article on Publisher Site

Abstract

A major transduction pathway for nitric oxide (NO) is stimulation of soluble guanylyl cyclase and the generation of cyclic GMP (cGMP). In the central nervous system, the NO–cGMP pathway has previously been associated primarily with synapses, particularly glutamatergic synapses. We report here that NO caused a large increase in the levels of cGMP in a central white matter tract devoid of synapses, namely in the rat isolated optic nerve. Cyclic GMP immunohistochemistry indicated that this response was confined to the axons. Accordingly, nerves previously subjected to 1 h of oxygen/glucose deprivation, which leads to irreversible axonal damage, displayed an 80% reduction in their subsequent capacity to generate cGMP in response to NO and a corresponding reduction in the numbers of cGMP‐immunostained axons. Protection of the axon cGMP response against this insult was achieved by omission of Ca2 + or Na + from the incubation medium, and by the pharmacological agents tetrodotoxin, lamotrigine, BW619C89 and BW1003C87, all of which protect axonal structure from oxygen/glucose deprivation‐induced damage. The results suggest that the NO–cGMP pathway has a hitherto unsuspected function in the optic nerve. Additionally, the expression of NO‐stimulated guanylyl cyclase in optic nerve axons provides a simple, sensitive and specific marker of their functional integrity that is likely to be valuable in investigating the mechanisms responsible for axon degeneration in ischaemia and other conditions.

Journal

European Journal of NeuroscienceWiley

Published: Dec 1, 1999

References

  • Axon conduction and survival in CNS white matter during energy deprivation: a developmental study
    Fern, Fern; Davis, Davis; Waxman, Waxman; Ransom, Ransom
  • Nitric oxide signaling in the central nervous system
    Garthwaite, Garthwaite; Boulton, Boulton
  • Cellular origins of cyclic GMP responses to excitatory amino acid receptor agonists in rat cerebellum in vitro
    Garthwaite, Garthwaite; Garthwaite, Garthwaite
  • Nitric oxide‐mediated cGMP synthesis in oligodendrocytes in the developing rat brain
    Tanaka, Tanaka; Markerink van Ittersum, Markerink van Ittersum; Steinbusch, Steinbusch; de Vente, de Vente

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