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.
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.
Faculté de Pharmacie, Université Paris Sud 11, F-92296 Châtenay-Malabry, France.
Pierre
P
Maurois
Nicole
N
Pages
Pierre
P
Bac
Michèle
M
German-Fattal
Geneviève
G
Agnani
Bernadette
B
Delplanque
Jean
J
Durlach
Jacques
J
Poupaert
Joseph
J
Vamecq
D000161:Acoustic Stimulation / Q000009:adverse effects; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D001393:Azoles / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D054833:Isoindoles; D008274:Magnesium / Q000008:administration & dosage / Q000494:pharmacology*; D008275:Magnesium Deficiency / Q000150:complications* / Q000188:drug therapy; D051379:Mice; D016202:N-Methylaspartate / Q000633:toxicity*; D016566:Organoselenium Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D012640:Seizures / Q000139:chemically induced* / Q000209:etiology
D000975:Antioxidants; D001393:Azoles; D054833:Isoindoles; D016566:Organoselenium Compounds; C042986:ebselen; D016202:N-Methylaspartate; D008274:Magnesium