PMID- 22886995 OWN - NLM STAT- MEDLINE DCOM- 20130422 LR - 20220330 IS - 1097-4644 (Electronic) IS - 0730-2312 (Linking) VI - 114 IP - 1 DP - 2013 Jan TI - The release of glutamate from cortical neurons regulated by BDNF via the TrkB/Src/PLC-gamma1 pathway. PG - 144-51 LID - 10.1002/jcb.24311 [doi] AB - The brain-derived neurotrophic factor (BDNF) participates in the regulation of cortical neurons by influencing the release of glutamate. However, the specific mechanisms are unclear. Hence, we isolated and cultured the cortical neurons of Sprague Dawley rats. Specific inhibitors of TrkB, Src, PLC-gamma1, Akt, and MEK1/2 (i.e., K252a, PP2, U73122, LY294002, and PD98059, respectively) were used to treat cortical neurons and to detect the glutamate release from cortical neurons stimulated with BDNF. BDNF significantly increased glutamate release, and simultaneously enhanced phosphorylation levels of TrkB, Src, PLC-gamma, Akt, and Erk1/2. For BDNF-stimulated cortical neurons, K252a inhibited glutamate release and inhibited the phosphorylation levels of TrkB, Src, PLC-gamma, Erk1/2, and Akt (P < 0.05). PP2 reduced the glutamate release from BDNF-stimulated cortical neurons (P < 0.05) and inhibited the phosphorylation levels of TrkB and PLC-gamma1 (P < 0.05). However, PP2 had no effect on the phosphorylation levels of Erk1/2 or Akt (P > 0.05). U73122 inhibited the glutamate release from BDNF-stimulated cortical neurons, but had no influence on the phosphorylation levels of TrkB, Src, Erk1/2, or Akt (P > 0.05). LY294002 and PD98059 did not affect the BDNF-stimulated glutamate release and did not inhibit the phosphorylation levels of TrkB, Src, or PLC-gamma1. In summary, BDNF stimulated the glutamate release from cortical neurons via the TrkB/Src/PLC-gamma1 signaling pathway. CI - Copyright (c) 2012 Wiley Periodicals, Inc. FAU - Zhang, Zitao AU - Zhang Z AD - Department of Spine Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China. FAU - Fan, Jin AU - Fan J FAU - Ren, Yongxin AU - Ren Y FAU - Zhou, Wei AU - Zhou W FAU - Yin, Guoyong AU - Yin G LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Cell Biochem JT - Journal of cellular biochemistry JID - 8205768 RN - 0 (AG 1879) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Carbazoles) RN - 0 (Chromones) RN - 0 (Enzyme Inhibitors) RN - 0 (Estrenes) RN - 0 (Flavonoids) RN - 0 (Indole Alkaloids) RN - 0 (Morpholines) RN - 0 (Pyrimidines) RN - 0 (Pyrrolidinones) RN - 112648-68-7 (1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione) RN - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one) RN - 3KX376GY7L (Glutamic Acid) RN - 97161-97-2 (staurosporine aglycone) RN - EC 2.7.10.1 (Receptor, trkB) RN - EC 2.7.10.2 (src-Family Kinases) RN - EC 3.1.4.3 (Phospholipase C gamma) RN - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/antagonists & inhibitors/genetics/*metabolism MH - Carbazoles/pharmacology MH - Cerebral Cortex/cytology/drug effects/*metabolism MH - Chromones/pharmacology MH - Embryo, Mammalian MH - Enzyme Inhibitors/pharmacology MH - Estrenes/pharmacology MH - Flavonoids/pharmacology MH - Gene Expression Regulation/drug effects MH - Glutamic Acid/biosynthesis/*metabolism MH - Indole Alkaloids/pharmacology MH - Morpholines/pharmacology MH - Neurons/cytology/drug effects/*metabolism MH - Phospholipase C gamma/antagonists & inhibitors/genetics/metabolism MH - Phosphorylation/drug effects MH - Primary Cell Culture MH - Pyrimidines/pharmacology MH - Pyrrolidinones/pharmacology MH - Rats MH - Rats, Sprague-Dawley MH - Receptor, trkB/antagonists & inhibitors/genetics/metabolism MH - Signal Transduction/drug effects MH - src-Family Kinases/antagonists & inhibitors/genetics/metabolism EDAT- 2012/08/14 06:00 MHDA- 2013/04/23 06:00 CRDT- 2012/08/14 06:00 PHST- 2012/05/25 00:00 [received] PHST- 2012/07/26 00:00 [accepted] PHST- 2012/08/14 06:00 [entrez] PHST- 2012/08/14 06:00 [pubmed] PHST- 2013/04/23 06:00 [medline] AID - 10.1002/jcb.24311 [doi] PST - ppublish SO - J Cell Biochem. 2013 Jan;114(1):144-51. doi: 10.1002/jcb.24311.