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DEVELOPMENTAL LEAD (PB) CHANGES AND IN HIPPOCAMPAL FUNCTION.
Citation:
GILBERT, M. E. AND S. M. LASLEY. DEVELOPMENTAL LEAD (PB) CHANGES AND IN HIPPOCAMPAL FUNCTION. Presented at Society of Toxicology, San Diego, CA, March 05 - 09, 2006.
Description:
Childhood lead (Pb) exposure has long been associated with reduced IQ, impaired cognitive function, and more recently increases in violence and aggression. We have studied the disruptive effects of developmental Pb exposure on an electrophysiological model of memory, hippocampal long-term potentiation (LTP). LTP represents the physiological alterations that occur at the synaptic level with learning and is a widely accepted model of the synaptic basis of memory. Both in vivo and in vitro assessments following developmental Pb exposure have revealed impairments in this form of synaptic memory. Threshold for induction was increased and magnitude of evoked LTP was reduced by Pb. The duration of LTP assessed over the course of several weeks was reduced in adult rats exposed continuously to Pb since birth. LTP in the hippocampus is dependent upon glutamatergic transmission and requires the activation of postsynaptic NMDA glutamate receptors. Presynaptically, impairment in LTP may stem from the effects of Pb to diminish transmitter release, actions that have been well documented in in vitro preparations. We have demonstrated Pb-induced reductions in glutamate and GABA release in the hippocampus of the intact animal using in vivo microdialysis. Postsynaptically, changes in NMDA receptor subunit expression have also been described which may contribute to altered LTP expression. Another form of impaired plasticity involving the addition of new granule cells to the hippocampal formation of the adult brain has been recently described. We have demonstrated that in adulthood, survival of newly generated neurons is compromised in the hippocampus of developmentally Pb-exposed rats. Neurogenesis may contribute to learning and memory or may serve to replace cells that die as the result of disease or injury. Evidence of an association between hippocampal neurogenesis and affective disorders has also been mounting. An impaired ability to replace neurons as a result of early Pb exposure may exacerbate adult-onset neurospychiatric or neurodegenerative disorders. (Funded by USEPA, NIEHS. Does not reflect US EPA policy).