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Brain‐derived neurotrophic factor uses CREB and Egr3 to regulate NMDA receptor levels in cortical neurons
Author(s) -
Kim Julia H.,
Roberts Daniel S.,
Hu Yinghui,
Lau Garrick C.,
BrooksKayal Amy R.,
Farb David H.,
Russek Shelley J.
Publication year - 2012
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2011.07555.x
Subject(s) - creb , brain derived neurotrophic factor , neurotrophic factors , neuroscience , nmda receptor , neurotransmission , trk receptor , neurotrophin , tropomyosin receptor kinase b , biology , glutamate receptor , excitatory postsynaptic potential , receptor , microbiology and biotechnology , transcription factor , inhibitory postsynaptic potential , biochemistry , gene
J. Neurochem. (2012) 120 , 210–219. Abstract Regulation of gene expression via brain‐derived neurotrophic factor (BDNF) is critical to the development of the nervous system and may well underlie cognitive performance throughout life. We now describe a mechanism by which BDNF can exert its effects on postsynaptic receptor populations that may have relevance to both the normal and diseased brain where BDNF levels either rise or fall in association with changes in excitatory neurotransmission. Increased levels of NMDA receptors (NMDARs) occur in rat cortical neurons via synthesis of new NMDA receptor 1 (NR1) subunits. The majority of synthesis is controlled by binding of cAMP response element binding protein (CREB) and early growth response factor 3 (Egr3) to the core NR1 promoter ( NR1‐p ) region. BDNF‐mediated NR1 transcription depends upon induction of the mitogen‐activated protein kinase (MAPK) pathway through activation of the TrK‐B receptor. Taken together with the fact that NMDAR activation stimulates BDNF synthesis, our results uncover a feed‐forward gene regulatory network that may enhance excitatory neurotransmission to change neuronal behavior over time.