Intraventricular IL-17A Administration Activates Microglia and Alters Their Localization in the Mouse Embryo Cerebral Cortex

Sasaki, Takuma; Tome, Saki; Takei, Yosuke

doi:10.21203/rs.3.rs-24894/v1

Cited by 2 publications

(1 citation statement)

References 25 publications

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“…Recent evidence suggests that IL-17A is a possible mediator underpinning MIA-induced ASD pathogenesis. [5][6][7][8][9][10] MIA-induced abnormalities associated with ASD were reported to be completely rescued in offspring of poly(I:C)injected mothers pretreated with IL-17A blocking antibody. Additionally, direct injection of recombinant IL-17A into the fetal brain resulted in similar abnormalities in cortical…”

Section: Introductionmentioning

confidence: 99%

The Effects of Maternal Interleukin-17A on Social Behavior, Cognitive Function, and Depression-Like Behavior in Mice with Altered Kynurenine Metabolites

Murakami

Imamura

Kasahara

et al. 2021

Int J�Tryptophan�Res

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Viral infection and chronic maternal inflammation during pregnancy are correlated with a higher prevalence of autism spectrum disorder (ASD). However, the pathoetiology of ASD is not fully understood; moreover, the key molecules that can cross the placenta following maternal inflammation and contribute to the development of ASD have not been identified. Recently, the pro-inflammatory cytokine, interleukin-17A (IL-17A) was identified as a potential mediator of these effects. To investigate the impact of maternal IL-17A on offspring, C57BL/6J dams were injected with IL-17A-expressing plasmids via the tail vein on embryonic day 12.5 (E12.5), and maternal IL-17A was expressed continuously throughout pregnancy. By adulthood, IL-17A-injected offspring exhibited behavioral abnormalities, including social and cognitive defects. Additionally, maternal IL-17A promoted metabolism of the essential amino acid tryptophan, which produces several neuroactive compounds and may affect fetal neurodevelopment. We observed significantly increased levels of kynurenine in maternal serum and fetal plasma. Thus, we investigated the effects of high maternal concentration of kynurenine on offspring by continuously administering mouse dams with kynurenine from E12.5 during gestation. Obviously, maternal kynurenine administration rapidly increased kynurenine levels in the fetal plasma and brain, pointing to the ability of kynurenine to cross the placenta and change the KP metabolites which are affected as neuroactive compounds in the fetal brain. Notably, the offspring of kynurenine-injected mice exhibited behavioral abnormalities similar to those observed in offspring of IL-17A-conditioned mice. Several tryptophan metabolites were significantly altered in the prefrontal cortex of the IL-17A-conditioned and kynurenine-injected adult mice, but not in the hippocampus. Even though we cannot exclude the possibility or other molecules being related to ASD pathogenesis and the presence of a much lower degree of pathway activation, our results suggest that increased kynurenine following maternal inflammation may be a key factor in changing the balance of KP metabolites in fetal brain during neuronal development and represents a therapeutic target for inflammation-induced ASD-like phenotypes.

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Section: Introductionmentioning

confidence: 99%

The Effects of Maternal Interleukin-17A on Social Behavior, Cognitive Function, and Depression-Like Behavior in Mice with Altered Kynurenine Metabolites

Murakami

Imamura

Kasahara

et al. 2021

Int J�Tryptophan�Res

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Վալպրոյաթթուն՝ Աուտիզմի Սպեկտրի Խանգարումների Մոդելավորման Մեջ

Բաղդասարյան

2024

MSEJ

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Autism spectrum disorders (ASD) are neurodevelopmental disorders, characterized by impaired social interaction, repetitive behaviors, and restricted interests. The global prevalence of autism is approximately 1 in 100, with an increasing trend, particularly in North America, where it has reached 1 in 44. Despite extensive research, ASD’s pathogenesis remains unclear, though genetic, epigenetic, and environmental factors play key roles. In ASD animal models, such as those induced with valproic acid (VPA), researchers study ASD’s molecular, biochemical, and behavioral alterations. VPA, an antiepileptic drug with histone deacetylase inhibition properties, influences epigenetic regulation, leading to synaptic and neural development changes that resemble ASD traits in humans. Research highlights VPA’s effects on oxidative stress and synaptic changes, including impacts on proteins like VGAT and reductions in inhibitory synaptic transmission. Studies also suggest that antioxidants like astaxanthin may improve ASD-related behavioral symptoms in these models. This article aims to review synaptic changes in VPA-induced ASD models, with a focus on the role of VPA-induced oxidative stress and histone acetylation alterations. These findings offer insights into ASD pathogenesis, providing a foundation for exploring novel therapeutic approaches to mitigate ASD risks and improve treatment outcomes.

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Intraventricular IL-17A Administration Activates Microglia and Alters Their Localization in the Mouse Embryo Cerebral Cortex

Cited by 2 publications

References 25 publications

The Effects of Maternal Interleukin-17A on Social Behavior, Cognitive Function, and Depression-Like Behavior in Mice with Altered Kynurenine Metabolites

The Effects of Maternal Interleukin-17A on Social Behavior, Cognitive Function, and Depression-Like Behavior in Mice with Altered Kynurenine Metabolites

Վալպրոյաթթուն՝ Աուտիզմի Սպեկտրի Խանգարումների Մոդելավորման Մեջ

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