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

• Main Authors: Xu, Huixin (Author), Fame, Ryann M. (Author), Sutin, Jason (Author), Naranjo, Christopher (Author), Syau, Della (Author), Cui, Jin (Author), Shipley, Frederick B. (Author), Vernon, Amanda (Author), Gao, Fan (Author), Yong, Zhang (Author), Holtzman, Michael J. (Author), Heiman, Myriam (Author), Warf, Benjamin C. (Author), Lin, Pei-Yi (Author), Lehtinen, Maria K. (Author)
• Other Authors: Picower Institute for Learning and Memory (Contributor), Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences (Contributor), Broad Institute of MIT and Harvard (Contributor)
• Format: Article
• Language: English
• Published: Springer Science and Business Media LLC, 2021-04-06T15:35:42Z.
• Subjects: Article
• Online Access: Get fulltext

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.
NIH (Grants R01-AI130591 and R35-HL145242)