母体先兆子痫暴露后星形胶质细胞BCL2降低与子代血脑屏障破坏的关系

Abstract

Maternal preeclampsia (PE) contributes to neurodevelopmental disorders. However, the underlying molecular mechanism remains unclear. We investigated the potential biological regulatory mechanisms by establishing an animal model and primary cell culture. Data from the Adolescent Brain Cognitive Development human study revealed that the striatum mediates maternal PE and offspring behavioral disorders. In a rat PE model, offspring exhibited abnormal behaviors and reduced striatal vascular density, with disrupted blood-brain barrier (BBB) and swollen astrocytes. Primary astrocytes and brain microvascular endothelial cells (BMECs) were cultured. Astrocytes from PE-exposed offspring weakened tube-formation ability and BBB-related protein expression in BMECs. Transcript sequencing identified B-cell lymphoma 2 (BCL2) as a key neurodevelopmental gene affected by PE. Astrocytes with BCL2 knockdown weakened tube-formation and BBB-related protein expression in BMECs, matching PE offspring astrocytes. BCL2 knockdown in newborn rats resulted in disrupted BBB, and abnormal behaviors, similar to PE-exposed offspring. In summary, reduced astrocyte BCL2 levels contributed to BBB disruption in the striata of PE-exposed offspring, providing new insights into the mechanisms underlying neurodevelopmental disorders.