A choroid plexus apocrine secretion mechanism shapes CSF proteome and embryonic brain development.
bioRxiv : the preprint server for biology – January 16, 2024
Source: PubMed
Summary
The brain's protective fluid contains crucial proteins released through a newly discovered "cellular shedding" process. Scientists found that specialized cells in the choroid plexus release protein-rich cellular fragments into brain fluid, directly influencing neural development. When disrupted by maternal stress, illness, or certain drugs during pregnancy, this delicate process can alter brain development and affect future social behavior in offspring. This insight reveals how environmental factors during pregnancy may impact fetal brain formation.
Abstract
We discovered that apocrine secretion by embryonic choroid plexus (ChP) epithelial cells contributes to the cerebrospinal fluid (CSF) proteome and influences brain development in mice. The apocrine response relies on sustained intracellular calcium signaling and calpain-mediated cytoskeletal remodeling. It rapidly alters the embryonic CSF proteome, activating neural progenitors lining the brain's ventricles. Supraphysiological apocrine secretion induced during mouse development by maternal administration of a serotonergic 5HT2C receptor agonist dysregulates offspring cerebral cortical development, alters the fate of CSF-contacting neural progenitors, and ultimately changes adult social behaviors. Critically, exposure to maternal illness or to the psychedelic drug LSD during pregnancy also overactivates the ChP, inducing excessive secretion. Collectively, our findings demonstrate a new mechanism by which maternal exposure to diverse stressors disrupts in utero brain development.