Curcumin protects against glutamate excitotoxicity in rat cerebral cortical neurons by increasing brain-derived neurotrophic factor level and activating TrkB

Brain Res. 2008 May 19:1210:84-91. doi: 10.1016/j.brainres.2008.01.104. Epub 2008 Apr 16.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Antidepressive Agents / pharmacology
  • Antidepressive Agents / therapeutic use
  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Carbazoles / pharmacology
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Cells, Cultured
  • Cerebral Cortex / drug effects*
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / physiopathology
  • Curcumin / pharmacology*
  • Curcumin / therapeutic use
  • Depressive Disorder / drug therapy
  • Depressive Disorder / metabolism
  • Depressive Disorder / physiopathology
  • Dose-Response Relationship, Drug
  • Down-Regulation / drug effects
  • Down-Regulation / physiology
  • Enzyme Inhibitors / pharmacology
  • Glutamic Acid / toxicity*
  • Indole Alkaloids / pharmacology
  • Nerve Degeneration / drug therapy
  • Nerve Degeneration / metabolism
  • Nerve Degeneration / physiopathology
  • Neurons / drug effects*
  • Neurons / metabolism
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, trkB / drug effects*
  • Receptor, trkB / metabolism
  • Up-Regulation / drug effects

Substances

  • Antidepressive Agents
  • Brain-Derived Neurotrophic Factor
  • Carbazoles
  • Enzyme Inhibitors
  • Indole Alkaloids
  • Neuroprotective Agents
  • Glutamic Acid
  • staurosporine aglycone
  • Receptor, trkB
  • Curcumin