Altered CREB Binding to Activity-Dependent Genes in Serine Racemase Deficient Mice, a Mouse Model of Schizophrenia
Year: 2017
Type: article
Abstract: 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.
Source: ACS Chemical Neuroscience
Authors: Darrick T. Balu, Joseph T. Coyle
Institutions: Harvard University, McLean Hospital
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2769857584