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Maternal lead exposure induces sex-dependent cerebellar glial alterations and repetitive behaviors

Lead (Pb) is one of the most prevalent heavy metals we encounter daily. Although there are many reports regarding their toxic effects on humans, the effects of exposure to low lead concentrations throughout the pregnancy period on the offspring are not fully elucidated yet. This study aimed to inves...

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Autores principales: Choi, Juwon, Kim, Yoo Sung, Kim, Mi-Hye, Kim, Hee Jung, Yoon, Bo-Eun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9442054/
https://www.ncbi.nlm.nih.gov/pubmed/36072563
http://dx.doi.org/10.3389/fncel.2022.954807
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author Choi, Juwon
Kim, Yoo Sung
Kim, Mi-Hye
Kim, Hee Jung
Yoon, Bo-Eun
author_facet Choi, Juwon
Kim, Yoo Sung
Kim, Mi-Hye
Kim, Hee Jung
Yoon, Bo-Eun
author_sort Choi, Juwon
collection PubMed
description Lead (Pb) is one of the most prevalent heavy metals we encounter daily. Although there are many reports regarding their toxic effects on humans, the effects of exposure to low lead concentrations throughout the pregnancy period on the offspring are not fully elucidated yet. This study aimed to investigate the cellular mechanisms that occur in response to lead exposure. To this end, we administered lead-containing water to pregnant mice from the day of conception till delivery or till day 28 postnatally. Furthermore, we performed neurodevelopmental disorder-related behavior tests and RNA-sequencing analysis. We used both genders for all experiments because neurodevelopmental disorders usually show several sex-dependent differences. The results revealed increased levels of gliosis in the cerebella of lead-exposed pups compared to those in littermates belonging to the control group. Additionally, we observed altered behaviors of male mice in the autism spectrum disorder-related tests. RNA-sequencing results revealed changes in gamma-aminobutyric acid (GABA) signaling in the lead-exposed mouse model. Specifically, the lead-exposed male mice showed decreased monoamine oxidase B and increased levels of diamine oxidase enzyme, which is related to the synthesis of GABA in astrocytes. These findings demonstrate sex-dependent basal developmental changes in glial cells and an increased prevalence of autistic-like behaviors in the young pups of mothers exposed to lead during pregnancy.
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spelling pubmed-94420542022-09-06 Maternal lead exposure induces sex-dependent cerebellar glial alterations and repetitive behaviors Choi, Juwon Kim, Yoo Sung Kim, Mi-Hye Kim, Hee Jung Yoon, Bo-Eun Front Cell Neurosci Neuroscience Lead (Pb) is one of the most prevalent heavy metals we encounter daily. Although there are many reports regarding their toxic effects on humans, the effects of exposure to low lead concentrations throughout the pregnancy period on the offspring are not fully elucidated yet. This study aimed to investigate the cellular mechanisms that occur in response to lead exposure. To this end, we administered lead-containing water to pregnant mice from the day of conception till delivery or till day 28 postnatally. Furthermore, we performed neurodevelopmental disorder-related behavior tests and RNA-sequencing analysis. We used both genders for all experiments because neurodevelopmental disorders usually show several sex-dependent differences. The results revealed increased levels of gliosis in the cerebella of lead-exposed pups compared to those in littermates belonging to the control group. Additionally, we observed altered behaviors of male mice in the autism spectrum disorder-related tests. RNA-sequencing results revealed changes in gamma-aminobutyric acid (GABA) signaling in the lead-exposed mouse model. Specifically, the lead-exposed male mice showed decreased monoamine oxidase B and increased levels of diamine oxidase enzyme, which is related to the synthesis of GABA in astrocytes. These findings demonstrate sex-dependent basal developmental changes in glial cells and an increased prevalence of autistic-like behaviors in the young pups of mothers exposed to lead during pregnancy. Frontiers Media S.A. 2022-08-22 /pmc/articles/PMC9442054/ /pubmed/36072563 http://dx.doi.org/10.3389/fncel.2022.954807 Text en Copyright © 2022 Choi, Kim, Kim, Kim and Yoon. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Choi, Juwon
Kim, Yoo Sung
Kim, Mi-Hye
Kim, Hee Jung
Yoon, Bo-Eun
Maternal lead exposure induces sex-dependent cerebellar glial alterations and repetitive behaviors
title Maternal lead exposure induces sex-dependent cerebellar glial alterations and repetitive behaviors
title_full Maternal lead exposure induces sex-dependent cerebellar glial alterations and repetitive behaviors
title_fullStr Maternal lead exposure induces sex-dependent cerebellar glial alterations and repetitive behaviors
title_full_unstemmed Maternal lead exposure induces sex-dependent cerebellar glial alterations and repetitive behaviors
title_short Maternal lead exposure induces sex-dependent cerebellar glial alterations and repetitive behaviors
title_sort maternal lead exposure induces sex-dependent cerebellar glial alterations and repetitive behaviors
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9442054/
https://www.ncbi.nlm.nih.gov/pubmed/36072563
http://dx.doi.org/10.3389/fncel.2022.954807
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