Molecular changes in glutamatergic synapses induced by Pb2+: association with deficits of LTP and spatial learning.
What are the molecular bases for the neurotoxicity that occurs after developmental exposure to low levels of Pb2+, and are these effects persistent and detrimental in adults? Our inability to understand specific mechanisms behind Pb2+ neurotoxicity has long been one of many problem areas of this preventable childhood disease. The sensitivity of the developing brain to Pb2+-induced neurotoxicity is an outcome of the many unique characteristics that comprise the developing central nervous system. The developing brain can be exposed to significant concentrations of Pb2+ during vulnerable periods of development such as synapse formation, gene and protein expression, and other diverse molecular changes associated with these processes. Recently, changes in NMDA receptor subunits were identified in animals that showed cognitive deficits induced by exposure to Pb2+. This molecular association is important because it provides new evidence in the characterization of developmental Pb2+ neurotoxicity that supports physiological findings of impairments in synaptic plasticity and behavior. This review updates information from molecular studies that can be directly associated with impairments of behavior and synaptic plasticity, and outlines the functional consequences of molecular differences in Pb2+-exposed animals that illuminate potential mechanisms of Pb2+-induced neurotoxicity.
Nihei
M K
MK
Department of Environmental Health Sciences, The Johns Hopkins University School of Hygiene and Public Health, Baltimore, MD 21205, USA.
Guilarte
T R
TR
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007854:Lead / Q000009:adverse effects*; D007858:Learning / Q000187:drug effects* / Q000502:physiology; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D017470:Receptors, Glutamate / Q000502:physiology*; D013569:Synapses / Q000187:drug effects* / Q000502:physiology
D017470:Receptors, Glutamate; D007854:Lead