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Modulation by magnesium of N-methyl-D-aspartate receptors in developing human brain
H Chahal1, S W D'Souza, A J Barson
1School of Biological Sciences, University of Manchester.
Summary
Infant brains show higher N-methyl-D-aspartate (NMDA) receptor binding, potentially indicating hyper-responsiveness to glutamate and glycine. Therapeutic NMDA receptor blockade in neonates may require increased magnesium sulfate concentrations.
Area of Science:
- Neuroscience
- Pharmacology
- Developmental Biology
Background:
- Glutamate N-methyl-D-aspartate (NMDA) receptors play crucial roles in synaptic plasticity and neuronal development.
- Age-related changes in NMDA receptor function can impact brain development and response to therapeutic interventions.
Purpose of the Study:
- To investigate age-related alterations in NMDA receptor binding.
- To examine the influence of glutamate, glycine, and magnesium (Mg2+) on NMDA receptor binding across different age groups.
Main Methods:
- Utilized [3H]MK-801 binding assays on human prefrontal cortex membrane preparations.
- Analyzed samples from neonate, infant, and adult necropsy brains.
- Measured the effects of L-glutamate, glycine, and Mg2+ sulphate on ligand binding.
Main Results:
- Neonatal brains exhibited the lowest [3H]MK-801 binding.
- Infant brains showed the highest binding, with greater stimulation by L-glutamate and glycine.
- Mg2+ inhibited binding, with higher IC50 values observed in neonatal brains compared to infant and adult brains.
Conclusions:
- Infant brains may possess an excess of NMDA receptors that are hyper-responsive to glutamate and glycine.
- Neonatal NMDA receptors might lack a normal complement of Mg2+ sites, affecting Mg2+ inhibition potency.
- Higher magnesium sulfate concentrations may be necessary for effective NMDA receptor blockade in neonates.