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Dysfunction of cortical synapse-specific mitochondria in developing rats exposed to lead and its amelioration by ascorbate supplementation.

ABSTRACT: Background:Lead (Pb) is a widespread environmental neurotoxin and its exposure even in minute quantities can lead to compromised neuronal functions. A developing brain is particularly vulnerable to Pb mediated toxicity and early-life exposure leads to permanent alterations in brain development and neuronal signaling and plasticity, culminating into cognitive and behavioral dysfunctions and elevated risk of neuropsychiatric disorders later in life. Nevertheless, the underlying biochemical mechanisms have not been completely discerned. Methods:Because of their ability to fulfill high energy needs and to act as calcium buffers in events of high intensity neuronal activity as well as their adaptive regulatory capability to match the requirements of the dynamicity of synaptic signaling, synapse-specific or synaptic mitochondria (SM) are critical for synaptic development, function and plasticity. Our aim for the present study hence was to characterize the effects of early-life Pb exposure on the functions of SM of prepubertal rats. For this purpose, employing a chronic model of Pb neurotoxicity, we exposed rat pups perinatally and postnatally to Pb and used a plethora of colorimetric and fluorometric assays for assessing redox and bioenergetic properties of SM. In addition, taking advantage of its ability as an antioxidant and as a metal chelator, we employed ascorbic acid (vitamin C) supplementation as an ameliorative therapeutic strategy against Pb-induced neurotoxicity and dysfunction of SM. Results:Our results suggest that early-life exposure to Pb leads to elevated oxidative stress in cortical SM with consequent compromises in its energy metabolism activity. Ascorbate supplementation resulted in significant recovery of Pb-induced oxidative stress and functional compromise of SM. Conclusion:Alterations in redox status and bioenergetic properties of SM could potentially contribute to the synaptic dysfunction observed in events of Pb neurotoxicity. Additionally, our study provides evidence for suitability of ascorbate as a significant ameliorative agent in tacking Pb neurotoxicity.

SUBMITTER: Ahmad F

PROVIDER: S-EPMC5868605 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Dysfunction of cortical synapse-specific mitochondria in developing rats exposed to lead and its amelioration by ascorbate supplementation.

Ahmad Faraz F Salahuddin Mohammad M Alamoudi Widyan W Acharya Sadananda S

Neuropsychiatric disease and treatment 20180321

<h4>Background</h4>Lead (Pb) is a widespread environmental neurotoxin and its exposure even in minute quantities can lead to compromised neuronal functions. A developing brain is particularly vulnerable to Pb mediated toxicity and early-life exposure leads to permanent alterations in brain development and neuronal signaling and plasticity, culminating into cognitive and behavioral dysfunctions and elevated risk of neuropsychiatric disorders later in life. Nevertheless, the underlying biochemical ...[more]

PMID: 29606875

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Project description:Background:Lead (Pb) is a persistent environmental neurotoxin and its exposure even in minute quantities has been known to induce neuronal defects. The immature brain is singularly sensitive to Pb neurotoxicity, and its exposure during development has permanent detrimental effects on the brain developmental trajectory and neuronal signaling and plasticity, culminating into compromises in the cognitive and behavioral attributes which persists even later in adulthood. Several molecular pathways have been implicated in the Pb-mediated disruption of neuronal signaling, including elevated oxidative stress, alterations in neurotransmitter biology, and mitochondrial dysfunction. Nevertheless, the neuronal targets and biochemical pathways underlying these Pb-mediated alterations in synaptic development and function have not been completely deduced. In this respect, recent studies have shown that synaptic signaling and its maintenance and plasticity are critically dependent on localized de novo protein translation at the synaptic terminals. Materials and methods:The present study hence aimed to assess the alterations in the synapse-specific translation induced by developmental Pb exposure. To this end, in vitro protein translation rate was analyzed in the hippocampal synaptoneurosomal fractions of rat pups pre- and postnatally exposed to Pb using a puromycin incorporation assay. Moreover, we evaluated the therapeutic effects of ascorbic acid supplementation against Pb-induced deficits in synapse-localized protein translation. Results:We observed a significant loss in the rates of de novo protein translation in synaptoneurosomes of Pb-exposed pups compared to age-matched control pups. Interestingly, ascorbate supplementation lead to an appreciable recovery in Pb-induced translational deficits. Moreover, the deficit in activity-dependent synaptic protein translation was found to correlate significantly with the increase in the blood Pb levels. Conclusion:Dysregulation of synapse-localized de novo protein translation is a potentially critical determinant of Pb-induced synaptic dysfunction and the consequent deficits in behavioral, social, and psychological attributes of the organisms. In addition, our study establishes ascorbate supplementation as a key ameliorative agent against Pb-induced neurotoxicity.

Dataset Information

Dysfunction of cortical synapse-specific mitochondria in developing rats exposed to lead and its amelioration by ascorbate supplementation.

Publications

Dysfunction of cortical synapse-specific mitochondria in developing rats exposed to lead and its amelioration by ascorbate supplementation.

Similar Datasets

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