Altered CREB Binding to Activity-Dependent Genes in Serine Racemase Deficient Mice, a Mouse Model of Schizophrenia.
Altered CREB Binding to Activity-Dependent Genes in Serine Racemase Deficient Mice, a Mouse Model of Schizophrenia.
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DOI：
10.1021/acschemneuro.7b00404
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发表时间：
2018-09-19
影响因子：
5
通讯作者：
Coyle JT
中科院分区：
文献类型：
--
作者：
Balu DT;Coyle JT
CAMP反应元件结合蛋白(cAMP-Response-Element-Binding Protein，CREB)是一种广泛表达于脑内的转录因子，通过调节基因表达来调节神经可塑性。钙通过N-甲基-D-天冬氨酸受体(NMDARs)内流是一种明确的机制，导致CREB依赖的基因表达增加，包括脑源性神经营养因子(BDNF)、microRNA-132和活性调节细胞骨架相关蛋白(Arc)。这些分子与精神分裂症的病理生理学有关。我们先前证明，丝氨酸消旋酶基因敲除(SR−/−)小鼠由于缺乏前脑NMDAR共激动剂D-丝氨酸而表现出NMDAR功能低下，其海马区CREB依赖基因的表达也减少。利用染色质免疫沉淀，我们在这里表明，在SR−/−小鼠中，与脑源性神经营养因子、microRNA132和Arc启动子区域结合的CREB较少。这些数据表明，SR−/−小鼠的NMDAR功能低下导致CREB与已知活性依赖基因的结合减少，进而导致它们的表达减少。
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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DOI：
10.1111/j.1601-183x.2010.00656.x
发表时间：
2011-03
期刊：
Genes, brain, and behavior
影响因子：
--
作者：
DeVito LM;Balu DT;Kanter BR;Lykken C;Basu AC;Coyle JT;Eichenbaum H
通讯作者：
Eichenbaum H
影响因子：
15.9
作者：
Korb E;Finkbeiner S
通讯作者：
Finkbeiner S
影响因子：
3.5
作者：
Balu, Darrick T.;Carlson, Gregory C.;Talbot, Konrad;Kazi, Hala;Hill-Smith, Tiffany E.;Easton, Rachel M.;Birnbaum, Morris J.;Lucki, Irwin
通讯作者：
Lucki, Irwin
影响因子：
11
作者：
Basu, A. C.;Tsai, G. E.;Coyle, J. T.
通讯作者：
Coyle, J. T.
影响因子：
5.3
作者：
Hashimoto, T;Bergen, SE;Lewis, DA
通讯作者：
Lewis, DA