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Cotransporter-mediated water transport underlying cerebrospinal fluid formation

Author

Listed:
  • Annette B. Steffensen

    (University of Copenhagen)

  • Eva K. Oernbo

    (University of Copenhagen)

  • Anca Stoica

    (University of Copenhagen)

  • Niklas J. Gerkau

    (Heinrich Heine University Duesseldorf)

  • Dagne Barbuskaite

    (University of Copenhagen)

  • Katerina Tritsaris

    (University of Copenhagen)

  • Christine R. Rose

    (Heinrich Heine University Duesseldorf)

  • Nanna MacAulay

    (University of Copenhagen)

Abstract

Cerebrospinal fluid (CSF) production occurs at a rate of 500 ml per day in the adult human. Conventional osmotic forces do not suffice to support such production rate and the molecular mechanisms underlying this fluid production remain elusive. Using ex vivo choroid plexus live imaging and isotope flux in combination with in vivo CSF production determination in mice, we identify a key component in the CSF production machinery. The Na+/K+/2Cl− cotransporter (NKCC1) expressed in the luminal membrane of choroid plexus contributes approximately half of the CSF production, via its unusual outward transport direction and its unique ability to directly couple water transport to ion translocation. We thereby establish the concept of cotransport of water as a missing link in the search for molecular pathways sustaining CSF production and redefine the current model of this pivotal physiological process. Our results provide a rational pharmacological target for pathologies involving disturbed brain fluid dynamics.

Suggested Citation

  • Annette B. Steffensen & Eva K. Oernbo & Anca Stoica & Niklas J. Gerkau & Dagne Barbuskaite & Katerina Tritsaris & Christine R. Rose & Nanna MacAulay, 2018. "Cotransporter-mediated water transport underlying cerebrospinal fluid formation," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04677-9
    DOI: 10.1038/s41467-018-04677-9
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    Cited by:

    1. Qiguang Wang & Xue Xia & Huan Zhang & Yue Li & Lei Zhu & Yulong Shi & Yuzhao Tang & Jian Cheng & Xuhui Hui & Huile Gao, 2025. "Targeting modulation of the choroid plexus blood-CSF barrier and CSF hypersecretion via lipid nanoparticle-mediated co-delivery of siRNA and resveratrol," Nature Communications, Nature, vol. 16(1), pages 1-15, December.

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