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The Antiepileptic Drug and Toxic Teratogen Valproic Acid Alters Microglia in an Environmental Mouse Model of Autism
Autism spectrum disorder (ASD), a neurodevelopmental condition affecting approximately 1 in 44 children in North America, is thought to be a connectivity disorder. Valproic acid (VPA) is a multi-target drug widely used to treat epilepsy. It is also a toxic teratogen as well as a histone deacetylase...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9319720/ https://www.ncbi.nlm.nih.gov/pubmed/35878284 http://dx.doi.org/10.3390/toxics10070379 |
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author | Triyasakorn, Korawin Ubah, Ubah Dominic Babah Roan, Brandon Conlin, Minsyusheen Aho, Ken Awale, Prabha S. |
author_facet | Triyasakorn, Korawin Ubah, Ubah Dominic Babah Roan, Brandon Conlin, Minsyusheen Aho, Ken Awale, Prabha S. |
author_sort | Triyasakorn, Korawin |
collection | PubMed |
description | Autism spectrum disorder (ASD), a neurodevelopmental condition affecting approximately 1 in 44 children in North America, is thought to be a connectivity disorder. Valproic acid (VPA) is a multi-target drug widely used to treat epilepsy. It is also a toxic teratogen as well as a histone deacetylase inhibitor, and fetal exposure to VPA increases the risk of ASD. While the VPA model has been well-characterized for behavioral and neuronal deficits including hyperconnectivity, microglia, the principal immune cells of CNS that regulate dendrite and synapse formation during early brain development, have not been well-characterized and may provide potential hints regarding the etiology of this disorder. Therefore, in this study, we determined the effect of prenatal exposure to VPA on microglial numbers during early postnatal brain development. We found that prenatal exposure to VPA causes a significant reduction in the number of microglia in the primary motor cortex (PMC) during early postnatal brain development, particularly at postnatal day 6 (P6) and postnatal day 10 (P10) in male mice. The early microglial reduction in the VPA model coincides with active cortical synaptogenesis and is significant because it may potentially play a role in mediating impaired connectivity in ASD. |
format | Online Article Text |
id | pubmed-9319720 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-93197202022-07-27 The Antiepileptic Drug and Toxic Teratogen Valproic Acid Alters Microglia in an Environmental Mouse Model of Autism Triyasakorn, Korawin Ubah, Ubah Dominic Babah Roan, Brandon Conlin, Minsyusheen Aho, Ken Awale, Prabha S. Toxics Communication Autism spectrum disorder (ASD), a neurodevelopmental condition affecting approximately 1 in 44 children in North America, is thought to be a connectivity disorder. Valproic acid (VPA) is a multi-target drug widely used to treat epilepsy. It is also a toxic teratogen as well as a histone deacetylase inhibitor, and fetal exposure to VPA increases the risk of ASD. While the VPA model has been well-characterized for behavioral and neuronal deficits including hyperconnectivity, microglia, the principal immune cells of CNS that regulate dendrite and synapse formation during early brain development, have not been well-characterized and may provide potential hints regarding the etiology of this disorder. Therefore, in this study, we determined the effect of prenatal exposure to VPA on microglial numbers during early postnatal brain development. We found that prenatal exposure to VPA causes a significant reduction in the number of microglia in the primary motor cortex (PMC) during early postnatal brain development, particularly at postnatal day 6 (P6) and postnatal day 10 (P10) in male mice. The early microglial reduction in the VPA model coincides with active cortical synaptogenesis and is significant because it may potentially play a role in mediating impaired connectivity in ASD. MDPI 2022-07-09 /pmc/articles/PMC9319720/ /pubmed/35878284 http://dx.doi.org/10.3390/toxics10070379 Text en © 2022 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 | Communication Triyasakorn, Korawin Ubah, Ubah Dominic Babah Roan, Brandon Conlin, Minsyusheen Aho, Ken Awale, Prabha S. The Antiepileptic Drug and Toxic Teratogen Valproic Acid Alters Microglia in an Environmental Mouse Model of Autism |
title | The Antiepileptic Drug and Toxic Teratogen Valproic Acid Alters Microglia in an Environmental Mouse Model of Autism |
title_full | The Antiepileptic Drug and Toxic Teratogen Valproic Acid Alters Microglia in an Environmental Mouse Model of Autism |
title_fullStr | The Antiepileptic Drug and Toxic Teratogen Valproic Acid Alters Microglia in an Environmental Mouse Model of Autism |
title_full_unstemmed | The Antiepileptic Drug and Toxic Teratogen Valproic Acid Alters Microglia in an Environmental Mouse Model of Autism |
title_short | The Antiepileptic Drug and Toxic Teratogen Valproic Acid Alters Microglia in an Environmental Mouse Model of Autism |
title_sort | antiepileptic drug and toxic teratogen valproic acid alters microglia in an environmental mouse model of autism |
topic | Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9319720/ https://www.ncbi.nlm.nih.gov/pubmed/35878284 http://dx.doi.org/10.3390/toxics10070379 |
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