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Exposure to Methylmercury at Juvenile Stage Worsens Autism-Like Symptoms in Adult BTBR T+tf/J Mice Due to Lack of Nuclear Factor Erythroid 2-Related Factor 2 Signaling Upregulation in Periphery and Brain

Autism spectrum disorder (ASD) is a multifaceted developmental condition that first appears in infancy. The condition is characterized by recurrent patterns in behavior and impairments in social and vocalization abilities. Methylmercury is a toxic environmental pollutant, and its derivatives are the...

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Autores principales: Algahtani, Mohammad M., Ahmad, Sheikh F., Alkharashi, Layla A., Al-Harbi, Naif O., Alanazi, Wael A., Alhamed, Abdullah S., Attia, Sabry M., Bakheet, Saleh A., Ibrahim, Khalid E., Nadeem, Ahmed
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10305371/
https://www.ncbi.nlm.nih.gov/pubmed/37368646
http://dx.doi.org/10.3390/toxics11060546
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author Algahtani, Mohammad M.
Ahmad, Sheikh F.
Alkharashi, Layla A.
Al-Harbi, Naif O.
Alanazi, Wael A.
Alhamed, Abdullah S.
Attia, Sabry M.
Bakheet, Saleh A.
Ibrahim, Khalid E.
Nadeem, Ahmed
author_facet Algahtani, Mohammad M.
Ahmad, Sheikh F.
Alkharashi, Layla A.
Al-Harbi, Naif O.
Alanazi, Wael A.
Alhamed, Abdullah S.
Attia, Sabry M.
Bakheet, Saleh A.
Ibrahim, Khalid E.
Nadeem, Ahmed
author_sort Algahtani, Mohammad M.
collection PubMed
description Autism spectrum disorder (ASD) is a multifaceted developmental condition that first appears in infancy. The condition is characterized by recurrent patterns in behavior and impairments in social and vocalization abilities. Methylmercury is a toxic environmental pollutant, and its derivatives are the major source of organic mercury to human beings. Inorganic mercury, which is released from a variety of pollutants into oceans, rivers, and streams, is transformed into methylmercury by bacteria and plankton in the water, which later builds up in fish and shellfish, and then enters humans through the consumption of fish and shellfish and increases the risk of developing ASD by disturbing the oxidant–antioxidant balance. However, there has been no prior research to determine the effect of juvenile exposure of methylmercury chloride on adult BTBR mice. Therefore, the current study evaluated the effect of methylmercury chloride administered during the juvenile stage on autism-like behavior (three-chambered sociability, marble burying, self-grooming tests) and oxidant–antioxidant balance (specifically Nrf2, HO-1, SOD-1, NF-kB, iNOS, MPO, and 3-nitrotyrosine) in the peripheral neutrophils and cortex of adult BTBR and C57BL/6 (B6) mice. Our results show that exposure to methylmercury chloride at a juvenile stage results in autism-like symptoms in adult BTBR mice which are related to a lack of upregulation of the Nrf2 signaling pathway as demonstrated by no significant changes in the expression of Nrf2, HO-1, and SOD-1 in the periphery and cortex. On the other hand, methylmercury chloride administration at a juvenile stage increased oxidative inflammation as depicted by a significant increase in the levels of NF-kB, iNOS, MPO, and 3-nitrotyrosine in the periphery and cortex of adult BTBR mice. This study suggests that juvenile exposure to methylmercury chloride contributes to the worsening of autism-like behavior in adult BTBR mice through the disruption of the oxidant–antioxidant balance in the peripheral compartment and CNS. Strategies that elevate Nrf2 signaling may be useful to counteract toxicant-mediated worsening of ASD and may improve quality of life.
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spelling pubmed-103053712023-06-29 Exposure to Methylmercury at Juvenile Stage Worsens Autism-Like Symptoms in Adult BTBR T+tf/J Mice Due to Lack of Nuclear Factor Erythroid 2-Related Factor 2 Signaling Upregulation in Periphery and Brain Algahtani, Mohammad M. Ahmad, Sheikh F. Alkharashi, Layla A. Al-Harbi, Naif O. Alanazi, Wael A. Alhamed, Abdullah S. Attia, Sabry M. Bakheet, Saleh A. Ibrahim, Khalid E. Nadeem, Ahmed Toxics Article Autism spectrum disorder (ASD) is a multifaceted developmental condition that first appears in infancy. The condition is characterized by recurrent patterns in behavior and impairments in social and vocalization abilities. Methylmercury is a toxic environmental pollutant, and its derivatives are the major source of organic mercury to human beings. Inorganic mercury, which is released from a variety of pollutants into oceans, rivers, and streams, is transformed into methylmercury by bacteria and plankton in the water, which later builds up in fish and shellfish, and then enters humans through the consumption of fish and shellfish and increases the risk of developing ASD by disturbing the oxidant–antioxidant balance. However, there has been no prior research to determine the effect of juvenile exposure of methylmercury chloride on adult BTBR mice. Therefore, the current study evaluated the effect of methylmercury chloride administered during the juvenile stage on autism-like behavior (three-chambered sociability, marble burying, self-grooming tests) and oxidant–antioxidant balance (specifically Nrf2, HO-1, SOD-1, NF-kB, iNOS, MPO, and 3-nitrotyrosine) in the peripheral neutrophils and cortex of adult BTBR and C57BL/6 (B6) mice. Our results show that exposure to methylmercury chloride at a juvenile stage results in autism-like symptoms in adult BTBR mice which are related to a lack of upregulation of the Nrf2 signaling pathway as demonstrated by no significant changes in the expression of Nrf2, HO-1, and SOD-1 in the periphery and cortex. On the other hand, methylmercury chloride administration at a juvenile stage increased oxidative inflammation as depicted by a significant increase in the levels of NF-kB, iNOS, MPO, and 3-nitrotyrosine in the periphery and cortex of adult BTBR mice. This study suggests that juvenile exposure to methylmercury chloride contributes to the worsening of autism-like behavior in adult BTBR mice through the disruption of the oxidant–antioxidant balance in the peripheral compartment and CNS. Strategies that elevate Nrf2 signaling may be useful to counteract toxicant-mediated worsening of ASD and may improve quality of life. MDPI 2023-06-20 /pmc/articles/PMC10305371/ /pubmed/37368646 http://dx.doi.org/10.3390/toxics11060546 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Algahtani, Mohammad M.
Ahmad, Sheikh F.
Alkharashi, Layla A.
Al-Harbi, Naif O.
Alanazi, Wael A.
Alhamed, Abdullah S.
Attia, Sabry M.
Bakheet, Saleh A.
Ibrahim, Khalid E.
Nadeem, Ahmed
Exposure to Methylmercury at Juvenile Stage Worsens Autism-Like Symptoms in Adult BTBR T+tf/J Mice Due to Lack of Nuclear Factor Erythroid 2-Related Factor 2 Signaling Upregulation in Periphery and Brain
title Exposure to Methylmercury at Juvenile Stage Worsens Autism-Like Symptoms in Adult BTBR T+tf/J Mice Due to Lack of Nuclear Factor Erythroid 2-Related Factor 2 Signaling Upregulation in Periphery and Brain
title_full Exposure to Methylmercury at Juvenile Stage Worsens Autism-Like Symptoms in Adult BTBR T+tf/J Mice Due to Lack of Nuclear Factor Erythroid 2-Related Factor 2 Signaling Upregulation in Periphery and Brain
title_fullStr Exposure to Methylmercury at Juvenile Stage Worsens Autism-Like Symptoms in Adult BTBR T+tf/J Mice Due to Lack of Nuclear Factor Erythroid 2-Related Factor 2 Signaling Upregulation in Periphery and Brain
title_full_unstemmed Exposure to Methylmercury at Juvenile Stage Worsens Autism-Like Symptoms in Adult BTBR T+tf/J Mice Due to Lack of Nuclear Factor Erythroid 2-Related Factor 2 Signaling Upregulation in Periphery and Brain
title_short Exposure to Methylmercury at Juvenile Stage Worsens Autism-Like Symptoms in Adult BTBR T+tf/J Mice Due to Lack of Nuclear Factor Erythroid 2-Related Factor 2 Signaling Upregulation in Periphery and Brain
title_sort exposure to methylmercury at juvenile stage worsens autism-like symptoms in adult btbr t+tf/j mice due to lack of nuclear factor erythroid 2-related factor 2 signaling upregulation in periphery and brain
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10305371/
https://www.ncbi.nlm.nih.gov/pubmed/37368646
http://dx.doi.org/10.3390/toxics11060546
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