期刊
NEURON GLIA BIOLOGY
卷 1, 期 -, 页码 275-281出版社
CAMBRIDGE UNIV PRESS
DOI: 10.1017/S1740925X05000141
关键词
alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionate receptor; D-serine; N-methyl-D-aspartate receptor; serine racemase
资金
- Public Health Service [MH18501]
- Research Scientist Award [DA00074]
- NATIONAL INSTITUTE OF MENTAL HEALTH [R37MH018501, R01MH018501] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON DRUG ABUSE [K05DA000074] Funding Source: NIH RePORTER
Abundant recent evidence favors a neurotransmitter/neuromodulator role for D-serine. D-serine is synthesized from L-serine by serine racemase in astrocytic glia that ensheath synapses, especially in regions of the brain that are enriched in NMDA-glutamate receptors. D-serine is more potent than glycine at activating the 'glycine' site of these receptors. Moreover, selective degradation of D-serine but not glycine by D-amino acid oxidase markedly reduces NMDA neurotransmission. D-serine appears to be released physiologically in response to activation by glutamate of AMPA-glutamate receptors oil D-serine-containing glia. This causes glutamate-receptor-interacting protein, which binds serine racemase, to stimulate enzyme activity and D-serine release. Thus, glutamate triggers the release of D-serine so that the two amino acids call act together on postsynaptic NMDA receptors. D-serine also plays a role in neural development, being released from Bergmann glia to chemokinetically enhance the migration of granule cell cerebellar neurons from the external to the internal granular layer.
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