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

Author

Listed:
  • Huixin Xu

    (Boston Children’s Hospital)

  • Ryann M. Fame

    (Boston Children’s Hospital)

  • Cameron Sadegh

    (Boston Children’s Hospital
    Massachusetts General Hospital and Harvard Medical School)

  • Jason Sutin

    (Boston Children’s Hospital, Harvard Medical School)

  • Christopher Naranjo

    (Harvard Medical School)

  • Syau

    (Harvard Medical School)

  • Jin Cui

    (Boston Children’s Hospital)

  • Frederick B. Shipley

    (Boston Children’s Hospital
    Harvard University)

  • Amanda Vernon

    (Broad Institute of MIT and Harvard
    Picower Institute for Learning and Memory
    Massachusetts Institute of Technology)

  • Fan Gao

    (Broad Institute of MIT and Harvard
    Picower Institute for Learning and Memory
    Massachusetts Institute of Technology
    Bioinformatics Resource Center in the Beckman Institute at Caltech)

  • Yong Zhang

    (Washington University)

  • Michael J. Holtzman

    (Washington University)

  • Myriam Heiman

    (Broad Institute of MIT and Harvard
    Picower Institute for Learning and Memory
    Massachusetts Institute of Technology)

  • Benjamin C. Warf

    (Boston Children’s Hospital)

  • Pei-Yi Lin

    (Boston Children’s Hospital, Harvard Medical School)

  • Maria K. Lehtinen

    (Boston Children’s Hospital
    Harvard University)

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.

Suggested Citation

  • Huixin Xu & Ryann M. Fame & Cameron Sadegh & Jason Sutin & Christopher Naranjo & Syau & Jin Cui & Frederick B. Shipley & Amanda Vernon & Fan Gao & Yong Zhang & Michael J. Holtzman & Myriam Heiman & Be, 2021. "Choroid plexus NKCC1 mediates cerebrospinal fluid clearance during mouse early postnatal development," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20666-3
    DOI: 10.1038/s41467-020-20666-3
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    Cited by:

    1. Shelei Pan & Peter H. Yang & Dakota DeFreitas & Sruthi Ramagiri & Peter O. Bayguinov & Carl D. Hacker & Abraham Z. Snyder & Jackson Wilborn & Hengbo Huang & Gretchen M. Koller & Dhvanii K. Raval & Gra, 2023. "Gold nanoparticle-enhanced X-ray microtomography of the rodent reveals region-specific cerebrospinal fluid circulation in the brain," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

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