Journal
NEUROCHEMISTRY INTERNATIONAL
Volume 52, Issue 8, Pages 1394-1401Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuint.2008.02.010
Keywords
cerebellum; cell death; development; nitric oxide
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Funding
- Biotechnology and Biological Sciences Research Council [BBS/A/00021] Funding Source: researchfish
- Biotechnology and Biological Sciences Research Council [BBS/A/00021] Funding Source: Medline
- Wellcome Trust Funding Source: Medline
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Nitric oxide is a diffusible messenger that plays a multitude of roles within the nervous system including modulation of cell viability. However, its role in regulating neuronal survival during a defined period of neurodevelopment has never been investigated. We discovered that expression of the messenger RNA for both neuronal and endothelial nitric oxide synthase increased in the early postnatal period in the cerebellum in vivo, whilst the expression of inducible nitric oxide synthase remained constant throughout this time in development. Whilst scavenging of nitric oxide was deleterious to the survival of early postnatal cerebellar granule neurons in vitro, this effect was lost in cultures derived at increasing postnatal ages. Conversely, sensitivity to exogenous nitric oxide increased with advancing postnatal age. Thus, we have shown that as postnatal development proceeds, cerebellar granule cells alter their in vitro survival responses to both nitric oxide inhibition and donation, revealing that the nitric oxide's effects on developing neurons vary with the stage of development studied. These findings have important consequences for our understanding of the role of nitric oxide during neuronal development. (C) 2008 Elsevier Ltd. All rights reserved.
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