Neurochemical aspects of hippocampal and cortical Pb2+ neurotoxicity
Guilarte, T.R.; Miceli, R.C.; Jett, D.A.
Neurotoxicology 15(3): 459-466
1994
ISSN/ISBN: 0161-813X PMID: 7854579 Document Number: 422657
The amino acid glutamate is the neurotransmitter used by most excitatory synapses in the mammalian brain. Glutamatergic synapses in the hippocampus and cerebral cortex play an important role in synaptic plasticity. In the developing brain, the interaction of neurotoxins with presynaptic and/ or postsynaptic sites on glutamatergic neurons could alter synaptic plasticity. Recent studies have shown that chronic lead (Pb-2+) exposure may impair neuronal processes underlying synaptic plasticity via a direct interaction with the N-Methyl-D-Aspartate (NMDA) glutamate receptor subtype. The NMDA receptor-ion channel complex regulates calcium influx and is involved in the initiation of changes in synaptic plasticity. In vitro and in vivo neurochemical studies have found that Pb-2+ has a marked inhibitory effect on the activation of the NMDA receptor-ion channel complex. Evidence indicates that the inhibitory effect of Pb-2+ on the NMDA receptor complex may be mediated by its interaction with a zinc regulatory site on the receptor complex. The ability of Pb-2+ to inhibit NMDA receptor-ion channel function was shown to be age-dependent and brain region-specific. The age-dependent effects of Pb-2+ on the NMDA receptor complex may help explain the selective toxicity of this heavy metal in the developing brain.