1. Curcumin Protects against NMDA-Induced Toxicity: A Possible Role for NR2A Subunit
- Author
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Roberta Cammarota, Lanfranco Leo, Claudio Frank, Monica Varano, Fiorella Malchiodi-Albedi, Giovanna Carnovale-Scalzo, Annamaria M Di Stasi, Chiara De Nuccio, Maria Balduzzi, Sergio Visentin, G Scorcia, Silvia Paradisi, Gian Carlo Bellenchi, Andrea Matteucci, and Cinzia Mallozzi
- Subjects
Programmed cell death ,Curcumin ,N-Methylaspartate ,Patch-Clamp Techniques ,Time Factors ,Blotting, Western ,Excitotoxicity ,Apoptosis ,Pharmacology ,medicine.disease_cause ,Hippocampus ,Receptors, N-Methyl-D-Aspartate ,Neuroprotection ,Retina ,chemistry.chemical_compound ,Pregnancy ,Excitatory Amino Acid Agonists ,In Situ Nick-End Labeling ,medicine ,Animals ,Patch clamp ,Rats, Wistar ,Receptor ,alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid ,Cells, Cultured ,Kainic Acid ,Dose-Response Relationship, Drug ,Retinal ,Immunohistochemistry ,Rats ,Neuroprotective Agents ,nervous system ,chemistry ,NMDA receptor ,Calcium ,Female ,Dizocilpine Maleate ,Excitatory Amino Acid Antagonists - Abstract
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 fluorometric recordings with Fura 2-AM were used to monitor [Ca(2+)](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 [Ca(2+)](i) rise, whole-cell patch-clamp experiments showed that a higher percentage of retinal neurons responded to NMDA with low amplitude current after curcumin treatment. In parallel, curcumin induced an increase in NMDAr subunit type 2A (NR2A) level, with kinetics closely correlated to time-course of neuroprotection and decrease in [Ca(2+)](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.
- Published
- 2011