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Taprenepag restores maternal–fetal interface homeostasis for the treatment of neurodevelopmental disorders

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Journal of Neuroinflammation

Published in:

Open Access 01-12-2024 | Valproate | Research

Taprenepag restores maternal–fetal interface homeostasis for the treatment of neurodevelopmental disorders

Authors: Kai Wang, Shufen Zhang, Yunxia Wang, Xiaomei Wu, Lijuan Wen, Tingting Meng, Xiangyu Jin, Sufen Li, Yiling Hong, Jia Ke, Yichong Xu, Hong Yuan, Fuqiang Hu

Published in: Journal of Neuroinflammation | Issue 1/2024

Abstract

Background and purpose

Neurodevelopmental disorders (NDDs) are characterized by abnormalities in brain development and neurobehaviors, including autism. The maternal–fetal interface (MFI) is a highly specialized tissue through which maternal factors affect fetal brain development. However, limited research exists on restoring and maintaining MFI homeostasis and its potential impact on NDDs. This study explores the role of placental indoleamine 2,3-dioxygenase (IDO-1) in MFI homeostasis and fetal brain development.

Experimental Approach

The maternal-fetal barrier was disrupted by sodium valproate (VPA) in pregnant mice, whose offspring show typical autism-like behaviors. Ultrastructural analysis and flow cytometric analysis were conducted to observe the morphological and immune system changes. Behavioral tests and immunofluorescence staining was used to investigate the ability and mechanism of taprenepag to alleviate the abnormal behaviors of VPA-exposed offspring and normalize the development of serotonergic neurons.

Key results

In VPA-exposed pregnant mice, the downregulation of IDO-1 led to maternal immune overactivation and disruption of maternal-fetal barrier, resulting in excessive 5-HT synthesis in the placenta. This process disrupted the development of the serotonergic neuronal system in the offspring, resulting in impaired development of serotonergic neurons, thalamocortical axons, and NDDs in the progeny. However, a single injection of taprenepag at E13.5 ultimately upregulated placental IDO-1 through amplifying the positive feedback loop COX-2/PGE₂/PTGER-2/IDO-1 and abolished these alterations.

Conclusion

Taprenepag improved autism-like behaviors in the offspring of VPA-exposed mice by addressing placental IDO-1 downregulation. This study highlights the potential of targeting IDO-1 to mitigate MFI disruption and NDD development.

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Title: Taprenepag restores maternal–fetal interface homeostasis for the treatment of neurodevelopmental disorders
Authors: Kai Wang
Shufen Zhang
Yunxia Wang
Xiaomei Wu
Lijuan Wen
Tingting Meng
Xiangyu Jin
Sufen Li
Yiling Hong
Jia Ke
Yichong Xu
Hong Yuan
Fuqiang Hu
Publication date: 01-12-2024
Publisher: BioMed Central
Keywords: Valproate
Neurodevelopmental Disorders
Neurodevelopmental Disorders
Published in: Journal of Neuroinflammation / Issue 1/2024
Electronic ISSN: 1742-2094
DOI: https://doi.org/10.1186/s12974-024-03300-7

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Taprenepag restores maternal–fetal interface homeostasis for the treatment of neurodevelopmental disorders

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