期刊
ACS CHEMICAL NEUROSCIENCE
卷 9, 期 9, 页码 2205-2209出版社
AMER CHEMICAL SOC
DOI: 10.1021/acschemneuro.7b00404
关键词
Serine racemase; D-serine; NMDA receptor; CREB; Arc; brain derived neurotrophic factor
资金
- [1K99MH099252-01A1]
- [5R00MH099252-04]
- [R01MH05190]
cAMP-response-element-binding protein (CREB) is a transcription factor ubiquitously expressed in the brain that regulates neuroplasticity by modulating gene expression. The influx of calcium through N-methyl-D-aspartate receptors (NMDARs) is a well-defined mechanism that leads to the increased expression of CREB-dependent genes, including brain derived neurotrophic factor (BDNF), microRNA-132, and activity-regulated cytoskeleton-associated protein (Arc). These molecules are implicated in the pathophysiology of schizophrenia. We previously demonstrated that serine racemase knockout (SR-/-) mice, which exhibit NMDAR hypofunction due to a lack of the forebrain NMDAR co-agonist D-serine, also have reduced expression of CREB-dependent genes in the hippocampus. Using chromatin immunoprecipitation, we show here that, in SR-/- mice, there is less CREB bound to the promoter regions of BDNF, microRNA-132, and Arc. These data suggest that NMDAR hypofunction in SR-/- mice leads to reduced CREB binding on known activity-dependent genes, in turn contributing to their reduced expression.
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