Synaptic plasticity in the CA1 and CA3 hippocampal region of pre- and postnatally lead-exposed rats

Gutowski, Martin; Altmann, L; Sveinsson, Karolina; Wiegand, Herbert

doi:10.1016/s0378-4274(98)00036-8

Cited by 24 publications

(13 citation statements)

References 31 publications

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“…The hypothesis that lead may cause persistent brain lesions is consistent with animal evidence suggesting that lead can cause cell death or changes to cellular architecture [4][5][6][7][8][9][10][11][12] including the formation of neurofibrillary tangles. 10,12 Moreover, glial acidic fibrillary protein, a cell-specific cytoskeletal intermediate filament protein that is an indicator of cell damage or death, increases in the hippocampus of animals dosed with lead.…”

Section: Neurology 2006;66:1476-1484supporting

confidence: 66%

Past adult lead exposure is linked to neurodegeneration measured by brain MRI

et al. 2006

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Section: Neurology 2006;66:1476-1484supporting

confidence: 66%

Past adult lead exposure is linked to neurodegeneration measured by brain MRI

et al. 2006

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“…In this respect it is important to determine the actual Pb 2+ concentrations in the brain. Although blood levels provide an index of recent exposure, they do not reflect (Guilarte and McGlothan, 1998;Gutowski et al, 1998;Cai et al, 2001) and are not simply related with the concentration in the brain. Pb 2+ concentration in the brain appears to be dependent on the animal age (Sui et al, 2000;Zhang et al, 2002), but independent of the brain region, with no selective accumulation in any brain area (Widzowski and Cory-Slechta, 1994, but see Nihei et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

“…Pb 2+ treatment was reported to impair LTP induced by high frequency stimulation following acute exposure in vitro (Hori et al, 1993;Carpenter et al, 1994) as well as in ex vivo approaches, using tissue taken from chronically exposed animals (Gutowski et al, 1998;Cai et al, 2001). In in vivo models Pb 2+ caused a decrease of LTP amplitude (Lasley et al, 1993;Gilbert et al, 1996;Ruan et al, 1998) and an elevation of LTP-threshold (Gilbert et al, 1996;.…”

Section: Models Of Synaptic Plasticitymentioning

confidence: 99%

“…However, more recent studies revealed a significantly lower value of IC 50 for Pb 2+ block of NMDA channel conduction (Lasley and Gilbert, 1999;Gavazzo et al, 2001). In addition there are evidences that NMDA-dependent forms of synaptic plasticity are more susceptible to chronic lead exposure than NMDA-independent processes, because the NMDA-independent mossy fiber potentiation in the CA3 region of the hippocampus was not influenced by lead treatment (Gutowski et al, 1998). Then the deficit in LTP in lead-exposed animals seems to have a postsynaptic locus and may involve NMDA channel inhibition.…”

Section: Models Of Synaptic Plasticitymentioning

confidence: 99%

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Molecular targets of lead in brain neurotoxicity

Marchetti

2003

neurotox res

151

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The detrimental effects of lead poisoning have been well known since ancient times, but some of the most severe consequences of exposure to this metal have only been described recently. Lead [Pb(II)] affects the higher functions of the central nervous system and undermines brain growth, preventing the correct development of cognitive and behavioral functions. As an established neurotoxin, Pb(II) crosses the blood-brain barrier rapidly and concentrates in the brain. The mechanisms of lead neurotoxicity are complex and still not fully understood, but recent findings recognized that both Ca(II) dependent proteins and neurotransmitters receptors represent significant targets for Pb(II). In particular, acute and chronic exposure to lead would predominantly affect two specific protein complexes: protein kinase C and the N-methyl-D-aspartate subtype of glutamate receptor. These protein complexes are deeply involved in learning and cognitive functions and are also thought to interact significantly with each other to mediate these functions. This review outlines the most recent hypotheses and evidences that link lead poisoning to impairment of these protein functions, as well as the in vitro experimental approaches that are most likely to provide information on basic mechanicistic processes.

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“…Mitochondria are organelles that are intricately involved in neurotransmission, as they provide energy for vesicular biogenesis, packaging, movement and release [28]. Mitochondria are typically synthesized in the cell body, are sent to the axonal terminal for energy and then sent back to the cell body for degradation [29].…”

Section: Introductionmentioning

confidence: 99%

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

Guariglia

Stansfield

McGlothan

et al. 2016

BMC Pharmacol Toxicol

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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.

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Synaptic plasticity in the CA1 and CA3 hippocampal region of pre- and postnatally lead-exposed rats

Cited by 24 publications

References 31 publications

Past adult lead exposure is linked to neurodegeneration measured by brain MRI

Past adult lead exposure is linked to neurodegeneration measured by brain MRI

Molecular targets of lead in brain neurotoxicity

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

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