Valproic acid-exposed astrocytes impair inhibitory synapse formation and function

Abstract Valproic acid (VPA) is widely prescribed to treat epilepsy. Maternal VPA use is, however, clinically restricted because of the severe risk that VPA may cause neurodevelopmental disorders in offspring, such as autism spectrum disorder. Understanding the negative action of VPA may help to pre...

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Autores principales:	Kotomi Takeda, Takuya Watanabe, Kohei Oyabu, Shuntaro Tsukamoto, Yuki Oba, Takafumi Nakano, Kaori Kubota, Shutaro Katsurabayashi, Katsunori Iwasaki
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/49024c82ea48486eb29280de2989831e
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spelling	oai:doaj.org-article:49024c82ea48486eb29280de2989831e2021-12-02T11:45:54ZValproic acid-exposed astrocytes impair inhibitory synapse formation and function10.1038/s41598-020-79520-72045-2322https://doaj.org/article/49024c82ea48486eb29280de2989831e2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-79520-7https://doaj.org/toc/2045-2322Abstract Valproic acid (VPA) is widely prescribed to treat epilepsy. Maternal VPA use is, however, clinically restricted because of the severe risk that VPA may cause neurodevelopmental disorders in offspring, such as autism spectrum disorder. Understanding the negative action of VPA may help to prevent VPA-induced neurodevelopmental disorders. Astrocytes play a vital role in neurodevelopment and synapse function; however, the impact of VPA on astrocyte involvement in neurodevelopment and synapse function has not been examined. In this study, we examined whether exposure of cultured astrocytes to VPA alters neuronal morphology and synapse function of co-cultured neurons. We show that synaptic transmission by inhibitory neurons was small because VPA-exposed astrocytes reduced the number of inhibitory synapses. However, synaptic transmission by excitatory neurons and the number of excitatory synapses were normal with VPA-exposed astrocytes. VPA-exposed astrocytes did not affect the morphology of inhibitory neurons. These data indicate that VPA-exposed astrocytes impair synaptogenesis specifically of inhibitory neurons. Our results indicate that maternal use of VPA would affect not only neurons but also astrocytes and would result in perturbed astrocyte-mediated neurodevelopment.Kotomi TakedaTakuya WatanabeKohei OyabuShuntaro TsukamotoYuki ObaTakafumi NakanoKaori KubotaShutaro KatsurabayashiKatsunori IwasakiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kotomi Takeda Takuya Watanabe Kohei Oyabu Shuntaro Tsukamoto Yuki Oba Takafumi Nakano Kaori Kubota Shutaro Katsurabayashi Katsunori Iwasaki Valproic acid-exposed astrocytes impair inhibitory synapse formation and function
description	Abstract Valproic acid (VPA) is widely prescribed to treat epilepsy. Maternal VPA use is, however, clinically restricted because of the severe risk that VPA may cause neurodevelopmental disorders in offspring, such as autism spectrum disorder. Understanding the negative action of VPA may help to prevent VPA-induced neurodevelopmental disorders. Astrocytes play a vital role in neurodevelopment and synapse function; however, the impact of VPA on astrocyte involvement in neurodevelopment and synapse function has not been examined. In this study, we examined whether exposure of cultured astrocytes to VPA alters neuronal morphology and synapse function of co-cultured neurons. We show that synaptic transmission by inhibitory neurons was small because VPA-exposed astrocytes reduced the number of inhibitory synapses. However, synaptic transmission by excitatory neurons and the number of excitatory synapses were normal with VPA-exposed astrocytes. VPA-exposed astrocytes did not affect the morphology of inhibitory neurons. These data indicate that VPA-exposed astrocytes impair synaptogenesis specifically of inhibitory neurons. Our results indicate that maternal use of VPA would affect not only neurons but also astrocytes and would result in perturbed astrocyte-mediated neurodevelopment.
format	article
author	Kotomi Takeda Takuya Watanabe Kohei Oyabu Shuntaro Tsukamoto Yuki Oba Takafumi Nakano Kaori Kubota Shutaro Katsurabayashi Katsunori Iwasaki
author_facet	Kotomi Takeda Takuya Watanabe Kohei Oyabu Shuntaro Tsukamoto Yuki Oba Takafumi Nakano Kaori Kubota Shutaro Katsurabayashi Katsunori Iwasaki
author_sort	Kotomi Takeda
title	Valproic acid-exposed astrocytes impair inhibitory synapse formation and function
title_short	Valproic acid-exposed astrocytes impair inhibitory synapse formation and function
title_full	Valproic acid-exposed astrocytes impair inhibitory synapse formation and function
title_fullStr	Valproic acid-exposed astrocytes impair inhibitory synapse formation and function
title_full_unstemmed	Valproic acid-exposed astrocytes impair inhibitory synapse formation and function
title_sort	valproic acid-exposed astrocytes impair inhibitory synapse formation and function
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/49024c82ea48486eb29280de2989831e
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Valproic acid-exposed astrocytes impair inhibitory synapse formation and function

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