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Title: Chronic early life lead (Pb2+) exposure alters presynaptic vesicle pools in hippocampal synapses.

Authors: Guariglia, Sara Rose; Stansfield, Kirstie H; McGlothan, Jennifer; Guilarte, Tomas R

Published In BMC Pharmacol Toxicol, (2016 Nov 02)

Abstract: 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. 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.In 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.We 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.In 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.

PubMed ID: 27802838 Exiting the NIEHS site

MeSH Terms: Age Factors; Animals; Drug Administration Schedule; Hippocampus/drug effects*; Hippocampus/ultrastructure; Lead/administration & dosage; Lead/toxicity*; Male; Presynaptic Terminals/drug effects*; Presynaptic Terminals/ultrastructure; Random Allocation; Rats; Rats, Long-Evans; Synapses/drug effects*; Synapses/ultrastructure; Synaptic Vesicles/drug effects*; Synaptic Vesicles/ultrastructure

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