Modulation by magnesium of N-methyl-D-aspartate receptors in developing human brain

Aim-To investigate age related alterations in glutamate N-methyl-D-aspartate (NMDA) receptor binding produced by the modulatory compounds glutamate, glycine, and magnesium (Mg2+) sulphate. Methods-The effects produced by glutamate plus glycine, and Mg2+ on the binding of [H-3]MK-801, a ligand for the N-methyl-D-aspartate ion channel phencyclidine site, were measured in membrane preparations made from prefrontal cortex from human neonate (n = 5), infant (n = 6), and adult (n = 6) necropsy brains. Results-Neonatal brains had the least [H-3]MK-801 binding, suggesting either a low density of NMDA receptors or a more restricted access of [H-3]MK-801 to cation channel sites. Infant brains had the most [H-3]MK-801 binding which was stimulated to a greater extent by L-glutamate (100 mu M) and glycine (10 mu M) than in neonatal and adult brains. Mg2+ invariably inhibited [H-3]MK-801 binding. However, the Mg2+ IC50 value was higher in neonatal brain (3.6 mM) than infant (1.4 mM) and adult (0.87 mM) brains. Conclusion-Infant brain may have excess NMDA receptors which are hyper responsive to glutamate and glycine. The lower potency of Mg2+ to inhibit [H-3]MK-801 binding in neonatal cortex may be because newborn babies have NMDA receptors without the normal complement of Mg2+ sites. The findings suggest that therapeutic NMDA receptor block in neonates requires higher concentrations of magnesium sulphate in brain tissue.