Cotransporter-mediated water transport underlying cerebrospinal fluid formation
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Cotransporter-mediated water transport underlying cerebrospinal fluid formation. / Steffensen, Annette B.; Oernbo, Eva K.; Stoica, Anca; Gerkau, Niklas J.; Barbuskaite, Dagne; Tritsaris, Katerina; Rose, Christine R.; MacAulay, Nanna.
In: Nature Communications, Vol. 9, No. 1, 2167, 2018.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Cotransporter-mediated water transport underlying cerebrospinal fluid formation
AU - Steffensen, Annette B.
AU - Oernbo, Eva K.
AU - Stoica, Anca
AU - Gerkau, Niklas J.
AU - Barbuskaite, Dagne
AU - Tritsaris, Katerina
AU - Rose, Christine R.
AU - MacAulay, Nanna
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
U2 - 10.1038/s41467-018-04677-9
DO - 10.1038/s41467-018-04677-9
M3 - Journal article
C2 - 29867199
AN - SCOPUS:85048131386
VL - 9
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 2167
ER -
ID: 197959338