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

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

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Abstract

PURPOSE. Curcumin, a phenolic compound extracted from the rhizome of Curcuma longa, was found to attenuate NMDAinduced 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 [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 NMDAinduced [Ca2+]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 [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. © 2011 The Association for Research in Vision and Ophthalmology, Inc.
Original languageEnglish
Pages (from-to)1070 - 1077
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Volume52
Issue number2
DOIs
Publication statusPublished - Feb 2011
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience
  • Medicine(all)

Cite this

Matteucci, A., Cammarota, R., Paradisi, S., Varano, M., Balduzzi, M., Leo, L., ... Malchiodi-Albedi, F. (2011). Curcumin protects against NMDA-induced toxicity: A possible role for NR2A subunit. Investigative Ophthalmology and Visual Science, 52(2), 1070 - 1077. https://doi.org/10.1167/iovs.10-5966