Some metals, which have already been shown to alter synaptic transmission, are discussed in this review. This review covers the effects of metals on signal transmission from the presynaptic to the postsynaptic membrane, as well as the effects on synaptic plasticity with an emphasis on learning and memory, since subtle alterations in synaptic transmission due to the interaction of metals may have profound toxic effects in the CNS. Therefore, we highlight the mechanisms by which metals and their compounds interfere with the processes of synaptic transmission and synaptic plasticity. These are crucial process and the basis of all higher cognitive functions including learning and memory. Postsynaptically the binding of neurotransmitters changes the membrane potential, resulting in a hyper- or depolarization of the neuron and in the generation of an action potential when the threshold potential is reached.

Synaptic transmission depends on the timely opening of membrane channels, the precise functioning of intracellular signaling pathways, and metabolic pathways involved in the synthesis and the release of neurotransmitters. At the presynaptic side of the synapse the incoming electrical signal, in from of action potentials, is transformed to a chemical signal in the form of neurotransmitter release. It is estimated that each neuron has approximately 7000 synapses. The human brain has about 10 11 neurons, which interconnect and “communicate” with each other through synapses. In this review, we will examine the effects of these metals in the CNS, specifically at the synapse. Since the uptake mechanisms of the body are not able to distinguish between “physiologically required” and harmful metals, the toxic metals absorbed consequently might interact with the functions of the central nervous system (CNS), liver, kidneys, and hematopoietic system, thus presenting a significant health hazard. For living systems, metals can be divided in those which are essential for life, such as cobalt (Co), copper (Cu), zinc (Zn), manganese (Mn), and iron (Fe) which are potentially toxic only at higher concentration, and those which have no known biological function, which can be toxic at all concentrations such as cadmium (Cd), chromium (Cr), mercury (Hg), and lead (Pb) (for all abbreviations used in the review please refer to the abbreviations section to facilitate reading, the names of the specific metals discussed are given in italics). They are taken up by organisms through inhalation or by ingestion of food and water contaminated with these metals. Therefore, a number of these metals enter our environment as a consequence of their widespread use in preservatives, biocides, and paints. Metals are used in their elementary form as well as in compounds for various human needs. Metals and their compounds are distributed in ecosystems as a result of natural processes as well as anthropogenic activities. The multiple effects of metals might occur simultaneously and are based on the specific metal species, metal concentrations, and the types of neurons involved.

Al 3+, Pb 2+, Cd 2+, and As 2 O 3 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. Zn 2+, Pb 2+, Cu 2+, Cd 2+, Ni 2+, Co 2+, Li 3+, Hg +, and methylmercury modulate NMDA, AMPA/kainate, and/or GABA receptors activity. Postsynaptically, processes associated with the binding of NT to their receptors, activation of channels, and degradation of NT are altered by metals. Many metals (e.g., Pb 2+, Cd 2+, and Hg +) also interact with intracellular signaling pathways. Presynaptically metal ions modulate neurotransmitter release through their interaction with synaptic vesicles, ion channels, and the metabolism of neurotransmitters (NT). This paper summarizes the evidence for metal interactions with synaptic transmission and synaptic plasticity. Metal neurotoxicity is a global health concern.

Cavorite poisoning