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Abstract

Background: Lead (Pb2+) is ubiquitously distributed in the environment and shows significant health effects in humans. In 1999 the WHO published a preliminary study on lead poisoning in the State of Qatar based on a survey conducted during 1995-96. Water, Food and Blood samples were collected. 19% of the 200 blood samples collected exceeded a critical lead content of 10ug/dl, while the highest level was reported in the youngest age group. 47 out of 450 water samples collected were above the WHO guideline level of 0.01mg/l. Of the 204 samples investigating processed food only 4 exceeded the limit. This study underlines that lead poisoning is a silent epidemic and a serious public health concern. Lead toxicity leads to impaired hematopoietic, nervous- and renal-system function. This study summarizes lead neurotoxicity and highlights how lead partially mimics the function of Ca2+ and therefore how it modifies synaptic transmission pre- and post-synaptically. As calcium (Ca2+) is an important signaling ion in many biochemical pathways, lead (Pb2+) has a high affinity to its binding sites and replaces calcium, resulting in a decrease calcium conductance, altered calcium-dependent signaling pathways, vesicular mobilization and vesicular formation. This presentation highlights the major-interactions of lead with the different targets sites on pre and postsynaptic terminal of the neuron. Methods: To understand the basic mechanism of lead toxicity a vast body of literature was screened and analyzed to summarize and understand the complex and multifactorial interactions of lead. The results were divided into two sections: pre-synaptic targets and the post- synaptic effects. Results: Lead targets multiple sites pre-synaptically like voltage-gated Ca2+-channels, Ca2+-ATPases, PKC, Calmodulin, signal cascades like the PLC system. Figures in the pre synaptic sections represent how the release of neurotransmitter is reduced by lead; beginning with the impairment of voltage-gated Ca2+-channel, lead interferes with calcium Ca2+-ATPase followed by the intracellular calcium de-regulation and lead inhibits the fusion of synaptic vesicle with the membrane and therefore the release of neuro-transmitter. Post-synaptic effects of lead result in the generation of the post-synaptic potential and synaptic-plasticity. This section is subdivided in four categories: synaptic transmission, effects on NMDA, long term effects and effects on long term potentiation. As (pre-synaptically) lead reduces the release of neuro-transmitter, post-synaptically the membrane depolarization will be smaller decreasing the likelihood that action potentials will be generated. Overall, lead reduces the chance of a successful generation of (post-synaptic) actions potentials and prevents to initiate processes which are crucial for learning and memory processes. Conclusion Lead mimics the action of the second messenger Ca2+, thereby disturbs the normal physiological function of Ca2+. This review helps to understand the basic mechanism underlying lead neurotoxicity and emphasize the importance of reducing lead contamination. A detailed review (with animated illustrations of pre- and post-synaptic effects of lead) has been recently published by Florea et al., in the Journal of Local and Global Health Science (2013:4).

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/content/papers/10.5339/qfarf.2013.BIOP-063
2013-11-20
2020-06-01
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