Open Access

Non-conventional apoptotic response to ionising radiation mediated by N-methyl D-aspartate receptors in immature neuronal cells

  • Authors:
    • Nada Samari
    • Louis De Saint-Georges
    • Giuseppe Pani
    • Sarah Baatout
    • Luc Leyns
    • Mohammed Abderrafi Benotmane
  • View Affiliations

  • Published online on: January 15, 2013     https://doi.org/10.3892/ijmm.2013.1245
  • Pages: 516-524
  • Copyright: © Samari et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

During cortical development, N-methyl D-aspartate (NMDA) receptors are highly involved in neuronal maturation and synapse establishment. Their implication in the phenomenon of excitotoxicity has been extensively described in several neurodegenerative diseases due to the permissive entry of Ca2+ ions and massive accumulation in the intracellular compartment, which is highly toxic to cells. Ionising radiation is also a source of stress to the cells, particularly immature neurons. Their capacity to induce cell death has been described for various cell types either by directly damaging the DNA or indirectly through the generation of reactive oxygen species responsible for the activation of a battery of stress response effectors leading in certain cases, to cell death. In this study, in order to determine whether a link exists between NMDA receptors-mediated excitotoxicity and radiation-induced cell death, we evaluated radiation-induced cell death in vitro and in vivo in maturing neurons during the fetal period. Cell death induction was assessed by TUNEL, caspase-3 activity and DNA ladder assays, with or without the administration of dizocilpine (MK-801), a non-competitive NMDA receptor antagonist which blocks neuronal Ca2+ influx. To further investigate the possible involvement of Ca2+-dependent enzyme activation, known to occur at high Ca2+ concentrations, we examined the protective effect of a calpain inhibitor on cell death induced by radiation. Doses ranging from 0.2 to 0.6 Gy of X-rays elicited a clear apoptotic response that was prevented by the injection of dizocilpine (MK-801) or calpain inhibitor. These data demonstrate the involvement of NMDA receptors in radiation-induced neuronal death by the activation of downstream effectors, including calpain-related pathways. An increased apoptotic process elicited by radiation, occurring independently of the normal developmental scheme, may eliminate post-mitotic but immature neuronal cells and deeply impair the establishment of the neuronal network, which in the case of cortical development is critical for cognitive capacities.
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March 2013
Volume 31 Issue 3

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Samari N, De Saint-Georges L, Pani G, Baatout S, Leyns L and Benotmane MA: Non-conventional apoptotic response to ionising radiation mediated by N-methyl D-aspartate receptors in immature neuronal cells. Int J Mol Med 31: 516-524, 2013
APA
Samari, N., De Saint-Georges, L., Pani, G., Baatout, S., Leyns, L., & Benotmane, M.A. (2013). Non-conventional apoptotic response to ionising radiation mediated by N-methyl D-aspartate receptors in immature neuronal cells. International Journal of Molecular Medicine, 31, 516-524. https://doi.org/10.3892/ijmm.2013.1245
MLA
Samari, N., De Saint-Georges, L., Pani, G., Baatout, S., Leyns, L., Benotmane, M. A."Non-conventional apoptotic response to ionising radiation mediated by N-methyl D-aspartate receptors in immature neuronal cells". International Journal of Molecular Medicine 31.3 (2013): 516-524.
Chicago
Samari, N., De Saint-Georges, L., Pani, G., Baatout, S., Leyns, L., Benotmane, M. A."Non-conventional apoptotic response to ionising radiation mediated by N-methyl D-aspartate receptors in immature neuronal cells". International Journal of Molecular Medicine 31, no. 3 (2013): 516-524. https://doi.org/10.3892/ijmm.2013.1245