Choroid plexus NKCC1 mediates cerebrospinal fluid clearance during mouse early postnatal development

Huixin Xu, Ryann M. Fame, Cameron Sadegh, Jason Sutin, Christopher Naranjo, Syau Della Syau, Jin Cui, Frederick B. Shipley, Amanda Vernon, Fan Gao, Yong Zhang, Michael J. Holtzman, Myriam Heiman, Benjamin C. Warf, Pei Yi Lin, Maria K. Lehtinen

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Cerebrospinal fluid (CSF) provides vital support for the brain. Abnormal CSF accumulation, such as hydrocephalus, can negatively affect perinatal neurodevelopment. The mechanisms regulating CSF clearance during the postnatal critical period are unclear. Here, we show that CSF K+, accompanied by water, is cleared through the choroid plexus (ChP) during mouse early postnatal development. We report that, at this developmental stage, the ChP showed increased ATP production and increased expression of ATP-dependent K+ transporters, particularly the Na+, K+, Cl, and water cotransporter NKCC1. Overexpression of NKCC1 in the ChP resulted in increased CSF K+ clearance, increased cerebral compliance, and reduced circulating CSF in the brain without changes in intracranial pressure in mice. Moreover, ChP-specific NKCC1 overexpression in an obstructive hydrocephalus mouse model resulted in reduced ventriculomegaly. Collectively, our results implicate NKCC1 in regulating CSF K+ clearance through the ChP in the critical period during postnatal neurodevelopment in mice.

Original languageEnglish
Article number447
JournalNature communications
Volume12
Issue number1
DOIs
StatePublished - Dec 1 2021

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