PMID- 18420184 OWN - NLM STAT- MEDLINE DCOM- 20080826 LR - 20131121 IS - 0006-8993 (Print) IS - 0006-8993 (Linking) VI - 1210 DP - 2008 May 19 TI - Curcumin protects against glutamate excitotoxicity in rat cerebral cortical neurons by increasing brain-derived neurotrophic factor level and activating TrkB. PG - 84-91 LID - 10.1016/j.brainres.2008.01.104 [doi] AB - Curcumin is a major active component isolated from Curcuma longa. Previously, we have reported its significant antidepressant effect. However, the mechanisms underlying the antidepressant effects are still obscure. In the present study, we explored the effect of curcumin against glutamate excitotoxicity, mainly focusing on the neuroprotective effects of curcumin on the expression of Brain-Derived Neurotrophic Factor (BDNF), which is deeply involved in the etiology and treatment of depression. Exposure of rat cortical neurons to 10 microM glutamate for 24 h caused a significant decrease in BDNF level, accompanied with reduced cell viability and enhanced cell apoptosis. Pretreatment of neurons with curcumin reversed the BDNF expression and cell viability in a dose- and time-dependent manner. However, K252a, a Trk receptor inhibitor which is known to inhibit the activity of BDNF, could block the survival-promoting effect of curcumin. In addition, the up-regulation of BDNF levels by curcumin was also suppressed by K252a. Taken together, these results suggest that the neuroprotective effect of curcumin might be mediated via BDNF/TrkB signaling pathway. FAU - Wang, Rui AU - Wang R AD - Department of Pharmacology, School of Basic Medical Sciences and State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100083, PR China. FAU - Li, Ying-Bo AU - Li YB FAU - Li, Yu-Hua AU - Li YH FAU - Xu, Ying AU - Xu Y FAU - Wu, Hong-Li AU - Wu HL FAU - Li, Xue-Jun AU - Li XJ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20080416 PL - Netherlands TA - Brain Res JT - Brain research JID - 0045503 RN - 0 (Antidepressive Agents) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Carbazoles) RN - 0 (Enzyme Inhibitors) RN - 0 (Indole Alkaloids) RN - 0 (Neuroprotective Agents) RN - 3KX376GY7L (Glutamic Acid) RN - 97161-97-2 (staurosporine aglycone) RN - EC 2.7.10.1 (Receptor, trkB) RN - IT942ZTH98 (Curcumin) SB - IM MH - Animals MH - Animals, Newborn MH - Antidepressive Agents/pharmacology/therapeutic use MH - Apoptosis/drug effects/physiology MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Carbazoles/pharmacology MH - Cell Survival/drug effects/physiology MH - Cells, Cultured MH - Cerebral Cortex/*drug effects/metabolism/physiopathology MH - Curcumin/*pharmacology/therapeutic use MH - Depressive Disorder/drug therapy/metabolism/physiopathology MH - Dose-Response Relationship, Drug MH - Down-Regulation/drug effects/physiology MH - Enzyme Inhibitors/pharmacology MH - Glutamic Acid/*toxicity MH - Indole Alkaloids/pharmacology MH - Nerve Degeneration/drug therapy/metabolism/physiopathology MH - Neurons/*drug effects/metabolism MH - Neuroprotective Agents/pharmacology/therapeutic use MH - Rats MH - Rats, Sprague-Dawley MH - Receptor, trkB/*drug effects/metabolism MH - Up-Regulation/drug effects EDAT- 2008/04/19 09:00 MHDA- 2008/08/30 09:00 CRDT- 2008/04/19 09:00 PHST- 2007/09/19 00:00 [received] PHST- 2008/01/24 00:00 [revised] PHST- 2008/01/28 00:00 [accepted] PHST- 2008/04/19 09:00 [pubmed] PHST- 2008/08/30 09:00 [medline] PHST- 2008/04/19 09:00 [entrez] AID - S0006-8993(08)00295-3 [pii] AID - 10.1016/j.brainres.2008.01.104 [doi] PST - ppublish SO - Brain Res. 2008 May 19;1210:84-91. doi: 10.1016/j.brainres.2008.01.104. Epub 2008 Apr 16.