Developmental lead (Pb)-induced deficits in hippocampal protein translation at the synapses are ameliorated by ascorbate supplementation

Faraz Ahmad,1 Mohammad Salahuddin,2 Khaldoon Alsamman,3 Abdulaziz A AlMulla,4 Khaled F Salama4 1School of Life Science, BS Abdur Rahman Crescent Institute of Science & Technology, Vandulur, Chennai 600048, India; 2Animal House Department, Institute for Research and Medical Consultations, Im...

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Main Authors: Ahmad F, Salahuddin M, Alsamman K, AlMulla AA, Salama KF
Format: Article
Language:English
Published: Dove Medical Press 2018-11-01
Series:Neuropsychiatric Disease and Treatment
Subjects:
Online Access:https://www.dovepress.com/developmental-lead-pb-induced-deficits-in-hippocampal-protein-translat-peer-reviewed-article-NDT
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author Ahmad F
Salahuddin M
Alsamman K
AlMulla AA
Salama KF
author_facet Ahmad F
Salahuddin M
Alsamman K
AlMulla AA
Salama KF
author_sort Ahmad F
collection DOAJ
description Faraz Ahmad,1 Mohammad Salahuddin,2 Khaldoon Alsamman,3 Abdulaziz A AlMulla,4 Khaled F Salama4 1School of Life Science, BS Abdur Rahman Crescent Institute of Science & Technology, Vandulur, Chennai 600048, India; 2Animal House Department, Institute for Research and Medical Consultations, Imam Abdurrahman Bin Faisal University, Dammam 31441, Saudi Arabia; 3Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Imam Abdurrahman Bin Faisal University, Dammam 31441, Saudi Arabia; 4Department of Environmental Health, College of Public Health, Imam Abdurrahman Bin Faisal University, Dammam 31441, Saudi Arabia 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. Keywords: synaptoneurosomes, heavy metal neurotoxicity, neuropsychiatric, blood lead level, puromycin 
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spelling doaj.art-ef849312ac464398947653740debb5772022-12-21T21:52:54ZengDove Medical PressNeuropsychiatric Disease and Treatment1178-20212018-11-01Volume 143289329842716Developmental lead (Pb)-induced deficits in hippocampal protein translation at the synapses are ameliorated by ascorbate supplementationAhmad FSalahuddin MAlsamman KAlMulla AASalama KFFaraz Ahmad,1 Mohammad Salahuddin,2 Khaldoon Alsamman,3 Abdulaziz A AlMulla,4 Khaled F Salama4 1School of Life Science, BS Abdur Rahman Crescent Institute of Science & Technology, Vandulur, Chennai 600048, India; 2Animal House Department, Institute for Research and Medical Consultations, Imam Abdurrahman Bin Faisal University, Dammam 31441, Saudi Arabia; 3Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Imam Abdurrahman Bin Faisal University, Dammam 31441, Saudi Arabia; 4Department of Environmental Health, College of Public Health, Imam Abdurrahman Bin Faisal University, Dammam 31441, Saudi Arabia 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. Keywords: synaptoneurosomes, heavy metal neurotoxicity, neuropsychiatric, blood lead level, puromycin https://www.dovepress.com/developmental-lead-pb-induced-deficits-in-hippocampal-protein-translat-peer-reviewed-article-NDTsynapticheavy metal neurotoxicityneuropsychiatricblood levelpuromycin
spellingShingle Ahmad F
Salahuddin M
Alsamman K
AlMulla AA
Salama KF
Developmental lead (Pb)-induced deficits in hippocampal protein translation at the synapses are ameliorated by ascorbate supplementation
Neuropsychiatric Disease and Treatment
synaptic
heavy metal neurotoxicity
neuropsychiatric
blood level
puromycin
title Developmental lead (Pb)-induced deficits in hippocampal protein translation at the synapses are ameliorated by ascorbate supplementation
title_full Developmental lead (Pb)-induced deficits in hippocampal protein translation at the synapses are ameliorated by ascorbate supplementation
title_fullStr Developmental lead (Pb)-induced deficits in hippocampal protein translation at the synapses are ameliorated by ascorbate supplementation
title_full_unstemmed Developmental lead (Pb)-induced deficits in hippocampal protein translation at the synapses are ameliorated by ascorbate supplementation
title_short Developmental lead (Pb)-induced deficits in hippocampal protein translation at the synapses are ameliorated by ascorbate supplementation
title_sort developmental lead pb induced deficits in hippocampal protein translation at the synapses are ameliorated by ascorbate supplementation
topic synaptic
heavy metal neurotoxicity
neuropsychiatric
blood level
puromycin
url https://www.dovepress.com/developmental-lead-pb-induced-deficits-in-hippocampal-protein-translat-peer-reviewed-article-NDT
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