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

International Journal of Molecular Sciences

Aleksandra Zawadzka¹  Magdalena Cieślik¹  Agata Adamczyk¹ 

[1] Department of Cellular Signalling, Mossakowski Medical Research Institute, Polish Academy of Sciences, Pawińskiego 5, 02-106 Warsaw, Poland;

关键词: autism;    maternal immune activation (MIA);    inflammation;    cytokines;    therapeutic strategy;   

DOI  :  10.3390/ijms222111516

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown