美国波士顿儿童医院和哈佛医学院Maria K. Lehtinen研究团队近日取得一项新成果。经过不懈努力，他们探明了小鼠脑发育过程中脉络丛大汗液分泌影响脑脊液蛋白质组。相关论文发表在2025年5月28日出版的《自然—神经科学》杂志上。

本研究发现胚胎ChP上皮细胞分泌大汗液是雌雄小鼠脑脊液蛋白质组和神经发育的关键调节因子。该团队证明了5-羟色胺能5-HT_2C受体的激活（通过WAY-161503）触发持续的Ca²⁺信号，驱动小鼠和人类ChP的大汗液分泌。这种分泌会改变脑脊液蛋白质组，刺激脑室内的神经祖细胞，改变它们的发育轨迹。在小鼠子宫内诱导ChP分泌会破坏神经祖细胞动力学、大脑皮质结构和后代行为。此外，疾病或妊娠期间暴露于麦角酸二乙胺会引起同母胚胎协调的ChP分泌。他们的发现揭示了ChP中一个影响大脑发育的基本分泌途径，强调了它的破坏如何对大脑健康产生持久的影响。

据介绍，脉络膜丛（ChP）调节脑脊液（CSF）的组成，为大脑发育提供必要的分子线索；然而，胚胎ChP的分泌机制仍不明确。

附：英文原文

Title: Choroid plexus apocrine secretion shapes CSF proteome during mouse brain development

Author: Courtney, Yael, Head, Joshua P., Dani, Neil, Chechneva, Olga V., Shipley, Frederick B., Zhang, Yong, Holtzman, Michael J., Sadegh, Cameron, Libermann, Towia A., Lehtinen, Maria K.

Issue&Volume: 2025-05-28

Abstract: The choroid plexus (ChP) regulates cerebrospinal fluid (CSF) composition, providing essential molecular cues for brain development; yet, embryonic ChP secretory mechanisms remain poorly defined. Here we identify apocrine secretion by embryonic ChP epithelial cells as a key regulator of the CSF proteome and neurodevelopment in male and female mice. We demonstrate that the activation of serotonergic 5-HT2C receptors (by WAY-161503) triggers sustained Ca2+ signaling, driving high-volume apocrine secretion in mouse and human ChP. This secretion alters the CSF proteome, stimulating neural progenitors lining the brain’s ventricles and shifting their developmental trajectory. Inducing ChP secretion in utero in mice disrupts neural progenitor dynamics, cerebral cortical architecture and offspring behavior. Additionally, illness or lysergic acid diethylamide exposure during pregnancy provokes coordinated ChP secretion in the mouse embryo. Our findings reveal a fundamental secretory pathway in the ChP that shapes brain development, highlighting how its disruption can have lasting consequences for brain health.

DOI: 10.1038/s41593-025-01972-9

Source: https://www.nature.com/articles/s41593-025-01972-9