Hindawi Publishing Corporation Journal of Toxicology Volume 2012, Article ID 132671, 42 pages doi:10.1155/2012/132671 Review Article Metal Toxicity at the Synapse: Presynaptic, Postsynaptic, and Long-Term Effects Sanah Sadiq, Zena Ghazala, Arnab Chowdhury, and Dietrich Busselberg¨ Weill Cornell Medical College in Qatar, Qatar Foundation—Education City, P.O. Box 24144, Doha, Qatar Correspondence should be addressed to Dietrich Busselberg,¨
[email protected] Received 9 May 2011; Accepted 5 July 2011 Academic Editor: David O. Carpenter Copyright © 2012 Sanah Sadiq et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Metal neurotoxicity is a global health concern. This paper summarizes the evidence for metal interactions with synaptic transmission and synaptic plasticity. Presynaptically metal ions modulate neurotransmitter release through their interaction with synaptic vesicles, ion channels, and the metabolism of neurotransmitters (NT). Many metals (e.g., Pb2+, Cd2+,andHg+)also interact with intracellular signaling pathways. Postsynaptically, processes associated with the binding of NT to their receptors, activation of channels, and degradation of NT are altered by metals. Zn2+, Pb2+, Cu2+, Cd2+, Ni2+, Co2+, Li3+, Hg+,and 3+ 2+ 2+ methylmercury modulate NMDA, AMPA/kainate, and/or GABA receptors activity. Al , Pb , Cd ,andAs2O3 also impair synaptic plasticity by targeting molecules such as CaM, PKC, and NOS as well as the transcription machinery involved in the maintenance of synaptic plasticity. The multiple effects of metals might occur simultaneously and are based on the specific metal species, metal concentrations, and the types of neurons involved.