How choroid plexus apocrine secretion shapes fetal brain development

The human brain, like the brain of other mammals, is known to start developing before birth, via a coordinated sequence of molecular and cellular processes. Neuroscience studies have found that the choroid plexus (ChP), a specialized brain structure that regulates the production of a liquid that nourishes the brain and spinal cord, plays a key role in the brain’s early development.

The liquid produced by this structure, referred to as cerebrospinal fluid (CSF), carries biochemical signals that support the development of neurons and shape their organization.

However, to date, the molecular processes through which this process supports the brain’s early development remain poorly understood. One possible mechanism involved could be a process called “apocrine secretion,” through which the ChP could release contents into the CSF.

Researchers at Boston Children’s Hospital, Harvard Medical School, University of California Davis and other institutes carried out a study aimed at shedding new light on the contribution of the ChP to the shaping of the mammalian brain pre-birth.

Their findings, published in Nature Neuroscience, suggest that a type of serotonin receptor called 5-HT2C helps trigger ChP apocrine secretion, which in turn shapes the formation of early brain cells and their subsequent organization.

“We’ve known for years that the CSF helps guide brain development, but we didn’t fully understand how it gets loaded with all those signals during embryogenesis,” Ya’el Courtney, first author of the paper, told Medical Xpress.

“Our lab became fascinated by the ChP, the structure that makes CSF, and wondered if it might actively secrete important instructions to the developing brain.”

The key objective of the recent study by Courtney and her colleagues was to uncover the processes through which the ChP in embryos sends proteins to the CSF. In addition, they wished to determine whether these processes are influenced by signals originating from the mother carrying the embryo.

“We studied how the ChP in developing mouse brains releases proteins into the CSF,” explained Courtney.

“To do this, we gave pregnant mice a drug that activates a serotonin receptor found in the ChP. This caused the ChP cells to release large blobs of material, kind of like cell ‘bubbles,’ into the CSF. We used imaging to watch this process happen in real time, and we tested the fluid to see which proteins were released. Then we looked at how these changes affected brain growth and behavior in the offspring.”

The team’s experiments involving mice showed that the activation of serotonergic 5-HT2C receptors prompted prolonged calcium signaling, which altered the proteins that the ChP introduces in CSF. These proteins in turn affect the development of cells in a mouse embryo’s early brain.

Notably, Courtney and her colleagues showed that the same process could also underpin the early development of the human brain. Their findings suggest that the human ChP can also be activated by exposure to illnesses during pregnancy or the intake of some serotonin-activating drugs, such as lysergic acid diethylamide (LSD), which can prompt excessive apocrine secretion and adversely impact the brain’s long-term development.

“We discovered a new way the embryonic brain gets exposed to important developmental signals through a secretory process in the ChP called apocrine secretion,” said Courtney.

“This process floods the CSF with proteins that help shape how brain cells grow and connect. But we also found that overstimulating this process using certain drugs during pregnancy, or during illness, can throw off brain development and lead to long-lasting behavioral changes.”

The results of this study offer new valuable insight into the molecular and neural processes that promote the healthy development of the brain before birth, which could inform future neuroscience research.

In addition, they highlight the need to conduct further studies exploring the effects of taking serotonin-activating medications and contracting illnesses that affect serotonin signaling during pregnancy on an embryo’s developing brain.

“We’re now interested in expanding our understanding of where in the developing brain these CSF signals from the ChP can actually reach—not just the cortex, but potentially other regions as well,” added Courtney.

“We’re also working to pinpoint which specific proteins in the ChP’s secretions are most important for brain development. Finally, we’re investigating how other maternal exposures, including serotonergic drugs, environmental toxins, or other potential teratogens, might dysregulate this secretory system during pregnancy.”

Written for you by our author Ingrid Fadelli, edited by Sadie Harley, and fact-checked and reviewed by Robert Egan—this article is the result of careful human work. We rely on readers like you to keep independent science journalism alive. If this reporting matters to you, please consider a donation (especially monthly). You’ll get an ad-free account as a thank-you.

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