Curcumin protects against glutamate excitotoxicity in rat cerebral cortical neurons by increasing brain-derived neurotrophic factor level and activating TrkB.
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.
Wang
Rui
R
Department of Pharmacology, School of Basic Medical Sciences and State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100083, PR China.
Li
Ying-Bo
YB
Li
Yu-Hua
YH
Xu
Ying
Y
Wu
Hong-Li
HL
Li
Xue-Jun
XJ
D000818:Animals; D000831:Animals, Newborn; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002227:Carbazoles / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D003474:Curcumin / Q000494:pharmacology* / Q000627:therapeutic use; D003866:Depressive Disorder / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018698:Glutamic Acid / Q000633:toxicity*; D026121:Indole Alkaloids / Q000494:pharmacology; D009410:Nerve Degeneration / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000187:drug effects* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D002227:Carbazoles; D004791:Enzyme Inhibitors; D026121:Indole Alkaloids; D018696:Neuroprotective Agents; D018698:Glutamic Acid; C049985:staurosporine aglycone; D020813:Receptor, trkB; D003474:Curcumin