title: Nitric oxide targets oligodendrocytes and promotes their morphological differentiation.
abstract: In the central nervous system, nitric oxide (NO) transmits signals from one neurone to another, or from neurones to astrocytes or blood vessels, but the possibility of oligodendrocytes being physiological NO targets has been largely ignored. By exploiting immunocytochemistry for cGMP, the second messenger generated on activation of NO receptors, oligodendrocytes were found to respond to both exogenous and endogenous NO in cerebellar slices from rats aged 8 days to adulthood. Atrial natriuretic peptide, which acts on membrane-associated guanylyl cyclase-coupled receptors, also raised oligodendrocyte cGMP in cerebellar slices. The main endogenous source of NO accessing oligodendrocytes appeared to be the neuronal NO synthase isoform, which was active even under basal conditions and in a manner that was independent of glutamate receptors. Oligodendrocytes in brainstem slices were also shown to be potential NO targets. In contrast, in the optic nerve, oligodendrocyte cGMP was raised by natriuretic peptides but not NO. When cultures of cerebral cortex were continuously exposed to low NO concentrations (estimated as 40-90 pM), oligodendrocytes responded with a striking increase in arborization. This stimulation of oligodendrocyte growth could be replicated by low concentrations of 8-bromo-cGMP (maximum effect at 1 µM). It is concluded that oligodendrocytes are probably widespread targets for physiological NO (or natriuretic peptide) signals, with the resulting rise in cGMP serving to enhance their growth and maturation. NO might help coordinate the myelination of axons to the ongoing level of neuronal activity during development and could potentially contribute to adaptive changes in myelination in the adult.
authors.affiliation: Wolfson Institute for Biomedical Research, University College London, London, WC1E 6BT, United Kingdom.
authors.forename: Giti
authors.initials: G
authors.lastname: Garthwaite
authors.forename: Kathryn
authors.initials: K
authors.lastname: Hampden-Smith
authors.forename: Gary W
authors.initials: GW
authors.lastname: Wilson
authors.forename: David A
authors.initials: DA
authors.lastname: Goodwin
authors.forename: John
authors.initials: J
authors.lastname: Garthwaite
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology / Q000254:growth & development* / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D045265:Natriuretic Peptides / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology / Q000502:physiology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D046509:Tissue Culture Techniques
chemical_list: D045265:Natriuretic Peptides; D047428:Protein Kinase Inhibitors; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; C496322:Nos1 protein, rat; C496315:Nos3 protein, mouse; D006152:Cyclic GMP
keywords: brainstem; cGMP; cerebellum; myelination; natriuretic peptide; optic nerve