PMID- 18234890 OWN - NLM STAT- MEDLINE DCOM- 20080219 LR - 20211027 IS - 1529-2401 (Electronic) IS - 0270-6474 (Print) IS - 0270-6474 (Linking) VI - 28 IP - 5 DP - 2008 Jan 30 TI - BHLHB2 controls Bdnf promoter 4 activity and neuronal excitability. PG - 1118-30 LID - 10.1523/JNEUROSCI.2262-07.2008 [doi] AB - Brain-derived neurotrophic factor (BDNF), via activation of TrkB receptors, mediates vital physiological functions in the brain, ranging from neuronal survival to synaptic plasticity, and has been implicated in the pathophysiology of neurodegenerative disorders. Although transcriptional regulation of the BDNF gene (Bdnf) has been extensively studied, much remains to be understood. We discovered a sequence within Bdnf promoter 4 that binds the basic helix-loop-helix protein BHLHB2 and is a target for BHLHB2-mediated transcriptional repression. NMDA receptor activation de-repressed promoter 4-mediated transcription and correlated with reduced occupancy of the promoter by BHLHB2 in cultured hippocampal neurons. Bhlhb2 gene -/- mice showed increased hippocampal exon 4-specific Bdnf mRNA levels compared with +/+ littermates under basal and activity-dependent conditions. Bhlhb2 knock-out mice also showed increased status epilepticus susceptibility, suggesting that BHLHB2 alters neuronal excitability. Together, these results support a role for BHLHB2 as a new modulator of Bdnf transcription and neuronal excitability. FAU - Jiang, Xueying AU - Jiang X AD - Section on Molecular Genetics, Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20892, USA. FAU - Tian, Feng AU - Tian F FAU - Du, Yang AU - Du Y FAU - Copeland, Neal G AU - Copeland NG FAU - Jenkins, Nancy A AU - Jenkins NA FAU - Tessarollo, Lino AU - Tessarollo L FAU - Wu, Xuan AU - Wu X FAU - Pan, Hongna AU - Pan H FAU - Hu, Xian-Zhang AU - Hu XZ FAU - Xu, Ke AU - Xu K FAU - Kenney, Heather AU - Kenney H FAU - Egan, Sean E AU - Egan SE FAU - Turley, Helen AU - Turley H FAU - Harris, Adrian L AU - Harris AL FAU - Marini, Ann M AU - Marini AM FAU - Lipsky, Robert H AU - Lipsky RH LA - eng GR - Z01 AA000325/ImNIH/Intramural NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, N.I.H., Intramural PT - Research Support, U.S. Gov't, Non-P.H.S. PL - United States TA - J Neurosci JT - The Journal of neuroscience : the official journal of the Society for Neuroscience JID - 8102140 RN - 0 (Basic Helix-Loop-Helix Transcription Factors) RN - 0 (Bhlhe40 protein, mouse) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Homeodomain Proteins) SB - IM MH - Animals MH - Basic Helix-Loop-Helix Transcription Factors/genetics/*physiology MH - Brain-Derived Neurotrophic Factor/genetics/*metabolism MH - Cells, Cultured MH - Female MH - Homeodomain Proteins/genetics/*physiology MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Mice, Transgenic MH - NIH 3T3 Cells MH - Neurons/metabolism/*physiology MH - Promoter Regions, Genetic/genetics/*physiology MH - Rats PMC - PMC6671398 EDAT- 2008/02/01 09:00 MHDA- 2008/02/20 09:00 PMCR- 2008/07/30 CRDT- 2008/02/01 09:00 PHST- 2008/02/01 09:00 [pubmed] PHST- 2008/02/20 09:00 [medline] PHST- 2008/02/01 09:00 [entrez] PHST- 2008/07/30 00:00 [pmc-release] AID - 28/5/1118 [pii] AID - 3313074 [pii] AID - 10.1523/JNEUROSCI.2262-07.2008 [doi] PST - ppublish SO - J Neurosci. 2008 Jan 30;28(5):1118-30. doi: 10.1523/JNEUROSCI.2262-07.2008.