Abstract
BackgroundLead (Pb2+) exposure has been shown to impair presynaptic neurotransmitter release in both in vivo and in vitro model systems. The mechanism by which Pb2+ impairs neurotransmitter release has not been fully elucidated. In previous work, we have shown that Pb2+ exposure inhibits vesicular release and reduces the number of fast-releasing sites in cultured hippocampal neurons. We have also shown that Pb2+ exposure inhibits vesicular release and alters the distribution of presynaptic vesicles in Shaffer Collateral – CA1 synapses of rodents chronically exposed to Pb2+ during development.MethodsIn the present study, we used transmission electron microscopy to examine presynaptic vesicle pools in Mossy Fiber-CA3 synapses and in Perforant Path-Dentate Gyrus synapses of rats to determine if in vivo Pb2+ exposure altered presynaptic vesicle distribution in these hippocampal regions. Data were analyzed using T-test for each experimental endpoint.ResultsWe found that Pb2+ exposure significantly reduced the number of vesicles in the readily releasable pool and recycling pool in Mossy Fiber-CA3 terminals. In both Mossy Fiber-CA3 terminals and in Perforant Path-Dentate Gyrus terminals, Pb2+ exposure significantly increased vesicle nearest neighbor distance in all vesicular pools (Rapidly Releasable, Recycling and Resting). We also found a reduction in the size of the postsynaptic densities of CA3 dendrites in the Pb2+ exposed group.ConclusionsIn our previous work, we have demonstrated that Pb2+ exposure impairs vesicular release in Shaffer Collateral - CA1 terminals of the hippocampus and that the number of docked vesicles in the presynaptic active zone was reduced. Our current data shows that Pb2+ exposure reduces the number of vesicles that are in proximity to release sites in Mossy Fiber- CA3 terminals. Furthermore, Pb2+ exposure causes presynaptic vesicles to be further from one another, in both Mossy Fiber- CA3 terminals and in Perforant Pathway – Dentate Gyrus terminals, which may interfere with vesicle movement and release. Our findings provide a novel in vivo mechanism by which Pb2+ exposure impairs vesicle dynamics and release in the hippocampus.
Highlights
Lead (Pb2+) exposure has been shown to impair presynaptic neurotransmitter release in both in vivo and in vitro model systems
Since we examined asymmetric synapses via identification of the postsynaptic density (PSD), which typically contain NMDA receptors, we thought that a creating a model with a Blood Lead Level (BLL) comparable to that which produces Pb2+ mediated effects on NMDA receptor would allow us to characterize the maximal effect of Pb2+ on vesicular pools
Blood Lead Level (BLL) and weight The Pb2+ exposure paradigm used in the present study does not produce any overt toxicity based on body weight gain
Summary
Lead (Pb2+) exposure has been shown to impair presynaptic neurotransmitter release in both in vivo and in vitro model systems. The mechanism by which Pb2+ impairs neurotransmitter release has not been fully elucidated. We have shown that Pb2+ exposure inhibits vesicular release and alters the distribution of presynaptic vesicles in Shaffer Collateral – CA1 synapses of rodents chronically exposed to Pb2+ during development. Mechanisms underlying the release of neurotransmitters are highly complex and require precise interactions between pre-synaptic membrane proteins, vesicular proteins, ions and energy [2]. Exposure to lead (Pb2+) has been shown to inhibit the release of neurotransmitters, including glutamate and γ-aminobutyric acid (GABA), in various in vivo, in vitro and ex vivo models [3,4,5,6].
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