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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Autores principales:	Ahmad F, Salahuddin M, Alsamman K, AlMulla AA, Salama KF
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	synaptic heavy metal neurotoxicity neuropsychiatric blood level puromycin Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/ef849312ac464398947653740debb577
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spelling	oai:doaj.org-article:ef849312ac464398947653740debb5772021-12-02T03:09:39ZDevelopmental lead (Pb)-induced deficits in hippocampal protein translation at the synapses are ameliorated by ascorbate supplementation1178-2021https://doaj.org/article/ef849312ac464398947653740debb5772018-11-01T00:00:00Zhttps://www.dovepress.com/developmental-lead-pb-induced-deficits-in-hippocampal-protein-translat-peer-reviewed-article-NDThttps://doaj.org/toc/1178-2021Faraz 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 Ahmad FSalahuddin MAlsamman KAlMulla AASalama KFDove Medical Pressarticlesynapticheavy metal neurotoxicityneuropsychiatricblood levelpuromycinNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol Volume 14, Pp 3289-3298 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	synaptic heavy metal neurotoxicity neuropsychiatric blood level puromycin Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
spellingShingle	synaptic heavy metal neurotoxicity neuropsychiatric blood level puromycin Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 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
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
format	article
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
title	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_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_sort	developmental lead (pb)-induced deficits in hippocampal protein translation at the synapses are ameliorated by ascorbate supplementation
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/ef849312ac464398947653740debb577
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Developmental lead (Pb)-induced deficits in hippocampal protein translation at the synapses are ameliorated by ascorbate supplementation

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