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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...

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Autores principales: Triyasakorn, Korawin, Ubah, Ubah Dominic Babah, Roan, Brandon, Conlin, Minsyusheen, Aho, Ken, Awale, Prabha S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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.
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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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