Abstract Title:

Curcumin protects against NMDA-induced toxicity: a possible role for NR2A subunit.

Abstract Source:

Invest Ophthalmol Vis Sci. 2010 Sep 22. Epub 2010 Sep 22. PMID: 20861489

Abstract Author(s):

Andrea Matteucci, Roberta Cammarota, Silvia Paradisi, Monica Varano, Maria Balduzzi, Lanfranco Leo, Gian C Bellenchi, Chiara De Nuccio, Giovanna Carnovale-Scalzo, Giovanni Scorcia, Claudio Frank, Cinzia Mallozzi, Annamaria M Di Stasi, Sergio Visentin, Fiorella Malchiodi-Albedi

Article Affiliation:

Cell Biology and Neuroscience, Istituto Superiore di Sanità, Rome, Italy.


Purpose: Curcumin, a phenolic compound extracted from the rhizome of Curcuma longa, was found to attenuate NMDA-induced excitotoxicity in primary retinal cultures. This study was conducted to further characterize curcumin neuroprotective ability and analyze its effects on NMDA receptor (NMDAr) . Methods: NMDAr modifications were analyzed in primary retinal cell cultures using immunocytochemistry, whole-cell patch-clamp recording and western blot analysis. Cell death was evaluated with the TUNEL assay in primary retinal and hippocampal cultures. Optical fluorimetric recordings with Fura 2-AM were utilized to monitor [Ca2+]i. Results: Curcumin dose- and time-dependently protected both retinal and hippocampal neurons against NMDA-induced cell death, confirming its anti-excitotoxic property. In primary retinal cultures, in line with the observed reduction of NMDA-induced [Ca2+]i rise, whole-cell patch-clamp experiments showed that a higher percentage of retinal neurons responded to NMDA with low amplitude current following curcumin treatment. In parallel, curcumin induced an increase in NMDAr subunit type 2A (NR2A) level, with a kinetic closely correlated to time-course of neuroprotection and decrease in [Ca2+]i. The relation between neuroprotection and NR2A level increase was also in line with the observation that curcumin neuroprotection required protein synthesis. Electrophysiology confirmed an increased activity of NR2A-containing NMDAr at the plasma membrane level. Conclusions: These results confirm the neuroprotective activity of curcumin against NMDA toxicity, possibly related to an increased level of NR2A, and encourage further studies for a possible therapeutic use of curcumin based on neuromodulation of NMDArs.

Study Type : In Vitro Study

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