Nitric oxide down-regulates brain-derived neurotrophic factor secretion in cultured hippocampal neurons
AUTOR(ES)
Canossa, Marco
FONTE
The National Academy of Sciences
RESUMO
The regulation of neurotrophin (NT) secretion is critical for many aspects of NT-mediated neuronal plasticity. Neurons release NTs by activity-regulated secretion pathways, initiated either by neurotransmitters and/or by existing NTs by a positive-feedback mechanism. This process depends on calcium release from intracellular stores. Little is known, however, about potential pathways that down-regulate NT secretion. Here we demonstrate that nitric oxide (NO) induces a rapid down-regulation of brain-derived neurotrophic factor (BDNF) secretion in cultured hippocampal neurons. Similar effects occur by activating a downstream target of intracellular NO, the soluble guanylyl cyclase, or by increasing the levels of its product, cGMP. Furthermore, down-regulation of BDNF secretion is mediated by cGMP-activated protein kinase G, which prevents calcium release from inositol 1,4,5-trisphosphate-sensitive stores. Our data indicate that the NO/cGMP/protein kinase G pathway represents a signaling mechanism by which neurons can rapidly down-regulate BDNF secretion and suggest that, in hippocampal neurons, NT secretion is finely tuned by both stimulatory and inhibitory signals.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=122510Documentos Relacionados
- Brain-derived neurotrophic factor mediates estradiol-induced dendritic spine formation in hippocampal neurons
- Essential role of brain-derived neurotrophic factor in adult hippocampal function
- Brain-derived neurotrophic factor rapidly enhances synaptic transmission in hippocampal neurons via postsynaptic tyrosine kinase receptors.
- Brain-derived neurotrophic factor regulates expression of androgen receptors in perineal motoneurons
- Hippocampal long-term potentiation is impaired in mice lacking brain-derived neurotrophic factor.