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

Faraz Ahmad,1,2 Mohammad Salahuddin,3 Widyan Alamoudi,2 Sadananda Acharya1 1Department of Public Health, College of Public Health, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia; 2Neuroscience Department, Institute for Research and Medical Consultations, Imam Abdulrahman Bin Faisal Un...

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Autores principales:	Ahmad F, Salahuddin M, Alamoudi W, Acharya S
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	synaptic oxidative damage heavy metal neurotoxicity neuropsychiatric mitochondrial bioenergetics mitochondrial membrane potential Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/14fef049f0bd42f5bd157a14812c4bc5
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spelling	oai:doaj.org-article:14fef049f0bd42f5bd157a14812c4bc52021-12-02T07:29:50ZDysfunction of cortical synapse-specific mitochondria in developing rats exposed to lead and its amelioration by ascorbate supplementation1178-2021https://doaj.org/article/14fef049f0bd42f5bd157a14812c4bc52018-03-01T00:00:00Zhttps://www.dovepress.com/dysfunction-of-cortical-synapse-specific-mitochondria-in-developing-ra-peer-reviewed-article-NDThttps://doaj.org/toc/1178-2021Faraz Ahmad,1,2 Mohammad Salahuddin,3 Widyan Alamoudi,2 Sadananda Acharya1 1Department of Public Health, College of Public Health, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia; 2Neuroscience Department, Institute for Research and Medical Consultations, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia; 3Animal House Department, Institute for Research and Medical Consultations, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia 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. Keywords: synaptic, oxidative damage, heavy metal neurotoxicity, neuropsychiatric, mitochondrial bioenergetics, mitochondrial membrane potentialAhmad FSalahuddin MAlamoudi WAcharya SDove Medical Pressarticlesynapticoxidative damageheavy metal neurotoxicityneuropsychiatricmitochondrial bioenergeticsmitochondrial membrane potentialNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol Volume 14, Pp 813-824 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	synaptic oxidative damage heavy metal neurotoxicity neuropsychiatric mitochondrial bioenergetics mitochondrial membrane potential Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
spellingShingle	synaptic oxidative damage heavy metal neurotoxicity neuropsychiatric mitochondrial bioenergetics mitochondrial membrane potential Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 Ahmad F Salahuddin M Alamoudi W Acharya S Dysfunction of cortical synapse-specific mitochondria in developing rats exposed to lead and its amelioration by ascorbate supplementation
description	Faraz Ahmad,1,2 Mohammad Salahuddin,3 Widyan Alamoudi,2 Sadananda Acharya1 1Department of Public Health, College of Public Health, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia; 2Neuroscience Department, Institute for Research and Medical Consultations, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia; 3Animal House Department, Institute for Research and Medical Consultations, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia 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. Keywords: synaptic, oxidative damage, heavy metal neurotoxicity, neuropsychiatric, mitochondrial bioenergetics, mitochondrial membrane potential
format	article
author	Ahmad F Salahuddin M Alamoudi W Acharya S
author_facet	Ahmad F Salahuddin M Alamoudi W Acharya S
author_sort	Ahmad F
title	Dysfunction of cortical synapse-specific mitochondria in developing rats exposed to lead and its amelioration by ascorbate supplementation
title_short	Dysfunction of cortical synapse-specific mitochondria in developing rats exposed to lead and its amelioration by ascorbate supplementation
title_full	Dysfunction of cortical synapse-specific mitochondria in developing rats exposed to lead and its amelioration by ascorbate supplementation
title_fullStr	Dysfunction of cortical synapse-specific mitochondria in developing rats exposed to lead and its amelioration by ascorbate supplementation
title_full_unstemmed	Dysfunction of cortical synapse-specific mitochondria in developing rats exposed to lead and its amelioration by ascorbate supplementation
title_sort	dysfunction of cortical synapse-specific mitochondria in developing rats exposed to lead and its amelioration by ascorbate supplementation
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/14fef049f0bd42f5bd157a14812c4bc5
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Dysfunction of cortical synapse-specific mitochondria in developing rats exposed to lead and its amelioration by ascorbate supplementation

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