British Journal of Nutrition (2009), 101, 317–321

Short Communication

Threshold to N-methyl-D-aspartate-induced seizures in mice undergoing chronic nutritional magnesium deprivation is lowered in a way partly
responsive to acute magnesium and antioxidant administrations

Pierre Maurois1,2†, Nicole Pages3†, Pierre Bac1,2, Miche`le German-Fattal1,2, Genevie`ve Agnani4, Bernadette Delplanque4, Jean Durlach5,

Jacques Poupaert6 and Joseph Vamecq7*

1Faculte´ de Pharmacie, Universite´ Paris Sud 11, F-92296 Chaˆtenay-Malabry, France
2CNRS UMR 8162, IFR 13, Centre Chirurgical Marie Lannelongue, F-92350 Le Plessis Robinson, France
3Laboratoire de Toxicologie, Faculte´ de Pharmacie, Universite´ Louis Pasteur, F-67401 Illkirch, France
4NMPA, University of Paris XI, Orsay, France
5SDRM, Universite´ Pierre et Marie Curie, Paris VI, Paris, France
6Deparment of Medicinal Chemistry, School of Pharmacy, UCL, Brussels, Belgium
7INSERM Univ 045131, EA1046 Lille, France

(Received 13 February 2008 – Revised 6 May 2008 – Accepted 6 May 2008 – First published online 16 June 2008)

Magnesium deficiency may be induced by a diet impoverished in magnesium. This nutritional deficit promotes chronic inflammatory and oxidative
stresses, hyperexcitability and, in mice, susceptibility to audiogenic seizures. Potentiation by low-magnesium concentrations of the opening of
N-methyl-D-aspartate (NMDA) receptor/calcium channel in in vitro and ex vivo studies, and responsiveness to magnesium of in vivo brain
injury states are now well established. By contrast, little or no specific attention has been, however, paid to the in vivo NMDA receptor function/
excitability in magnesium deficiency. The present work reports for the first time that, in mice undergoing chronic nutritional deprivation
in magnesium (35 v. 930 parts per million for 27 d in OF1 mice), NMDA-induced seizure threshold is significantly decreased (38% of normal
values). The attenuation in the drop of NMDA seizure threshold (percentage of reversal) was 58 and 20% upon acute intraperitoneal administrations
of magnesium chloride hexahydrate (28 mg magnesium/kg) and the antioxidant ebselen (20 mg/kg), respectively. In nutritionally magnesium-
deprived animals, audiogenic seizures are completely prevented by these compound doses. Taken as a whole, our data emphasise that
chronic magnesium deprivation in mice is a nutritional in vivo model for a lowered NMDA receptor activation threshold. This nutritional
model responds remarkably to acute magnesium supply and moderately to acute antioxidant administration.