Dysfunction of Cortical Synapse-specific Mitochondria in Developing Rats Exposed to Lead and Its Amelioration by Ascorbate Supplementation

Overview

Journal Neuropsychiatr Dis Treat

Publisher Dove Medical Press

Specialty Psychiatry

Date 2018 Apr 3

PMID 29606875

Citations 6

Authors

Faraz Ahmad

Mohammad Salahuddin

Widyan Alamoudi

Sadananda Acharya

Affiliations

Soon will be listed here.

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.

Citing Articles

Isolated Mitochondrial Preparations and Assays: A Powerful and Relevant Tool for Assessment of Brain (Patho)physiology.

Ahmad F, Ramamorthy S, Areeshi M, Ashraf G, Haque S Curr Neuropharmacol. 2023; 21(6):1433-1449.

PMID: 36872352 PMC: 10324330. DOI: 10.2174/1570159X21666230303123555.

MOLECULAR MECHANISMS OF LEAD NEUROTOXICITY.

Virgolini M, Aschner M Adv Neurotoxicol. 2021; 5:159-213.

PMID: 34263090 PMC: 8276936. DOI: 10.1016/bs.ant.2020.11.002.

Maternal Lead Exposure Impairs Offspring Learning and Memory via Decreased GLUT4 Membrane Translocation.

Zhao Z, Du K, Wang T, Wang J, Cao Z, Chen X Front Cell Dev Biol. 2021; 9:648261.

PMID: 33718391 PMC: 7947239. DOI: 10.3389/fcell.2021.648261.

(Ascorb)ing Pb Neurotoxicity in the Developing Brain.

Ahmad F, Liu P Antioxidants (Basel). 2020; 9(12).

PMID: 33371438 PMC: 7767447. DOI: 10.3390/antiox9121311.

Pre- and Neonatal Exposure to Lead (Pb) Induces Neuroinflammation in the Forebrain Cortex, Hippocampus and Cerebellum of Rat Pups.

Chibowska K, Korbecki J, Gutowska I, Metryka E, Tarnowski M, Goschorska M Int J Mol Sci. 2020; 21(3).

PMID: 32041252 PMC: 7037720. DOI: 10.3390/ijms21031083.

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