Molecular Neurobiology

, Volume 42, Issue 3, pp 151–160 | Cite as

Molecular Neurobiology of Lead (Pb2+): Effects on Synaptic Function



Lead (Pb2+) is a ubiquitous environmental neurotoxicant that continues to threaten public health on a global scale. Epidemiological studies have demonstrated detrimental effects of Pb2+ on childhood IQ at very low levels of exposure. Recently, a mechanistic understanding of how Pb2+ affects brain development has begun to emerge. The cognitive effects of Pb2+ exposure are believed to be mediated through its selective inhibition of the N-methyl-d-aspartate receptor (NMDAR). Studies in animal models of developmental Pb2+ exposure exhibit altered NMDAR subunit ontogeny and disruption of NMDAR-dependent intracellular signaling. Additional studies have reported that Pb2+ exposure inhibits presynaptic calcium (Ca2+) channels and affects presynaptic neurotransmission, but a mechanistic link between presynaptic and postsynaptic effects has been missing. Recent work has suggested that the presynaptic and postsynaptic effects of Pb2+ exposure are both due to inhibition of the NMDAR by Pb2+, and that the presynaptic effects of Pb2+ may be mediated by disruption of NMDAR activity-dependent signaling of brain-derived neurotrophic factor (BDNF). These findings provide the basis for the first working model to describe the effects of Pb2+ exposure on synaptic function. Here, we review the neurotoxic effects of Pb2+ exposure and discuss the known effects of Pb2+ exposure in light of these recent findings.


Lead Neurotoxicology NMDA Receptor BDNF Synaptogenesis Neurotransmission 


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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of Pharmacology and ToxicologyMichigan State UniversityEast LansingUSA
  2. 2.Department of Environmental Health Sciences, Mailman School of Public HealthColumbia UniversityNew YorkUSA

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