The Role of Maternal Immune Activation in the Pathogenesis of Autism: A Review of the Evidence, Proposed Mechanisms and Implications for Treatment

Autism spectrum disorder (ASD) is a neurodevelopmental disease that is characterized by a deficit in social interactions and communication, as well as repetitive and restrictive behaviors. Increasing lines of evidence suggest an important role for immune dysregulation and/or inflammation in the deve...

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Autores principales:	Aleksandra Zawadzka, Magdalena Cieślik, Agata Adamczyk
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	autism maternal immune activation (MIA) inflammation cytokines therapeutic strategy Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/af8053bfc7394d12ac89d6252797efd8
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spelling	oai:doaj.org-article:af8053bfc7394d12ac89d6252797efd82021-11-11T16:58:37ZThe Role of Maternal Immune Activation in the Pathogenesis of Autism: A Review of the Evidence, Proposed Mechanisms and Implications for Treatment10.3390/ijms2221115161422-00671661-6596https://doaj.org/article/af8053bfc7394d12ac89d6252797efd82021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11516https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Autism spectrum disorder (ASD) is a neurodevelopmental disease that is characterized by a deficit in social interactions and communication, as well as repetitive and restrictive behaviors. Increasing lines of evidence suggest an important role for immune dysregulation and/or inflammation in the development of ASD. Recently, a relationship between inflammation, oxidative stress, and mitochondrial dysfunction has been reported in the brain tissue of individuals with ASD. Some recent studies have also reported oxidative stress and mitochondrial abnormalities in animal models of maternal immune activation (MIA). This review is focused on the hypothesis that MIA induces microglial activation, oxidative stress, and mitochondrial dysfunction, a deleterious trio in the brain that can lead to neuroinflammation and neurodevelopmental pathologies in offspring. Infection during pregnancy activates the mother’s immune system to release proinflammatory cytokines, such as IL-6, TNF-α, and others. Furthermore, these cytokines can directly cross the placenta and enter the fetal circulation, or activate resident immune cells, resulting in an increased production of proinflammatory cytokines, including IL-6. Proinflammatory cytokines that cross the blood–brain barrier (BBB) may initiate a neuroinflammation cascade, starting with the activation of the microglia. Inflammatory processes induce oxidative stress and mitochondrial dysfunction that, in turn, may exacerbate oxidative stress in a self-perpetuating vicious cycle that can lead to downstream abnormalities in brain development and behavior.Aleksandra ZawadzkaMagdalena CieślikAgata AdamczykMDPI AGarticleautismmaternal immune activation (MIA)inflammationcytokinestherapeutic strategyBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11516, p 11516 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	autism maternal immune activation (MIA) inflammation cytokines therapeutic strategy Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	autism maternal immune activation (MIA) inflammation cytokines therapeutic strategy Biology (General) QH301-705.5 Chemistry QD1-999 Aleksandra Zawadzka Magdalena Cieślik Agata Adamczyk The Role of Maternal Immune Activation in the Pathogenesis of Autism: A Review of the Evidence, Proposed Mechanisms and Implications for Treatment
description	Autism spectrum disorder (ASD) is a neurodevelopmental disease that is characterized by a deficit in social interactions and communication, as well as repetitive and restrictive behaviors. Increasing lines of evidence suggest an important role for immune dysregulation and/or inflammation in the development of ASD. Recently, a relationship between inflammation, oxidative stress, and mitochondrial dysfunction has been reported in the brain tissue of individuals with ASD. Some recent studies have also reported oxidative stress and mitochondrial abnormalities in animal models of maternal immune activation (MIA). This review is focused on the hypothesis that MIA induces microglial activation, oxidative stress, and mitochondrial dysfunction, a deleterious trio in the brain that can lead to neuroinflammation and neurodevelopmental pathologies in offspring. Infection during pregnancy activates the mother’s immune system to release proinflammatory cytokines, such as IL-6, TNF-α, and others. Furthermore, these cytokines can directly cross the placenta and enter the fetal circulation, or activate resident immune cells, resulting in an increased production of proinflammatory cytokines, including IL-6. Proinflammatory cytokines that cross the blood–brain barrier (BBB) may initiate a neuroinflammation cascade, starting with the activation of the microglia. Inflammatory processes induce oxidative stress and mitochondrial dysfunction that, in turn, may exacerbate oxidative stress in a self-perpetuating vicious cycle that can lead to downstream abnormalities in brain development and behavior.
format	article
author	Aleksandra Zawadzka Magdalena Cieślik Agata Adamczyk
author_facet	Aleksandra Zawadzka Magdalena Cieślik Agata Adamczyk
author_sort	Aleksandra Zawadzka
title	The Role of Maternal Immune Activation in the Pathogenesis of Autism: A Review of the Evidence, Proposed Mechanisms and Implications for Treatment
title_short	The Role of Maternal Immune Activation in the Pathogenesis of Autism: A Review of the Evidence, Proposed Mechanisms and Implications for Treatment
title_full	The Role of Maternal Immune Activation in the Pathogenesis of Autism: A Review of the Evidence, Proposed Mechanisms and Implications for Treatment
title_fullStr	The Role of Maternal Immune Activation in the Pathogenesis of Autism: A Review of the Evidence, Proposed Mechanisms and Implications for Treatment
title_full_unstemmed	The Role of Maternal Immune Activation in the Pathogenesis of Autism: A Review of the Evidence, Proposed Mechanisms and Implications for Treatment
title_sort	role of maternal immune activation in the pathogenesis of autism: a review of the evidence, proposed mechanisms and implications for treatment
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/af8053bfc7394d12ac89d6252797efd8
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The Role of Maternal Immune Activation in the Pathogenesis of Autism: A Review of the Evidence, Proposed Mechanisms and Implications for Treatment

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