Advertisement

Aquaporin-1 deletion reduces osmotic water permeability and cerebrospinal fluid production

  • K. Oshio
  • Y. Song
  • A. S. Verkman
  • Geoffrey T. ManleyEmail author
Conference paper
Part of the Acta Neurochirurgica Supplements book series (NEUROCHIRURGICA, volume 86)

Abstract

Aquaporin-1 (AQP1) is a water channel that is strongly expressed at the ventricular-facing surface of choroid plexus epithelium. Using wildtype and AQP1 null mice, we developed novel methods to compare the water permeability in isolated choroid plexus, and cerebrospinal fluid (CSF) production in living mice. Osmoticallyinduced water transport was rapid in freshly isolated choroid plexus from wildtype mice as measured by a spatial-filtering optical method, and reduced by 5-fold by AQP1 deletion. CSF production, an isosmolar fluid secretion process, was measured by a dye dilution method involving fluid collections using a second microneedle introduced into the cisterna magna. CSF production in wildtype mice was (in μl/min) 0.37 ± 0.04 μl/min (control), 0.16 ± 0.03 μl/min (acetazolamide-treated) and 1.14 ± 0.15 μl/min (forskolin-treated), and reduced by up to 25% in AQP1 null mice. The impaired CSF production in AQP1 null mice provides direct functional evidence for the involvement of AQP1 in CSF formation.

Keywords

Null Mouse Choroid Plexus Nephrogenic Diabetes Insipidus Wildtype Mouse Osmotic Water Permeability 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Bering EA, Sato O (1963) Hydrocephalus: Changes in formation and absorption of cerebrospinal fluid within the cerebral ventricles. J Neurosurg 20: 1050–1063PubMedCrossRefGoogle Scholar
  2. 2.
    Davson H, Hollingsworth G, Segal M (1970) The mechanism of drainage of the cerebrospinal fluid. Brain 93: 665–678PubMedCrossRefGoogle Scholar
  3. 3.
    Farinas J, Kneen M, Moore M, Verkman AS (1997) Plasma membrane water permeability of cultured cells and epithelia measured by light microscopy with spatial filtering. J Gen Physiol 110: 283–296PubMedCrossRefGoogle Scholar
  4. 4.
    Hasegawa H, Lian SC, Finkbeiner WE, Verkman AS (1994) Extrarenal tissue distribution of CHIP28 water channels by in situ hybridization and antibody staining. Am J Physiol 266: C893–C903PubMedGoogle Scholar
  5. 5.
    Ma T, Yang B, Gillespie A, Carlson EJ, Epstein CJ, Verkman AS (1998) Severely impaired urinary concentrating ability in transgenic mice lacking aquaporin-1 water channels. J Biol Chem 273: 4296–4299PubMedCrossRefGoogle Scholar
  6. 6.
    Ma T, Song Y, Yang B, Gillespie A, Carlson EJ, Epstein CJ, Verkman AS (2000) Nephrogenic diabetes insipidus in mice deficient in aquaporin-3 water channels. Proc Natl Acad Sci USA 97: 4386–4391PubMedCrossRefGoogle Scholar
  7. 7.
    Manley GT, Fujimura M, Ma T, Noshita N, Filiz F, Bollen AW, Chan P, Verkman AS (2000) Aquaporin-4 deletion in mice reduces brain edema after acute water intoxication and ischemic stroke. Nat Med 6: 159–163PubMedCrossRefGoogle Scholar
  8. 8.
    Milhorat T (1972) Hydrocephalus and cerebrospinal fluid. Williams and Wilkins, BaltimoreGoogle Scholar
  9. 9.
    Milhorat T, Hammock M, Fenstermacher J, Levin V (1971) Cerebrospinal fluid production by the choroid plexus and brain. Science 173: 330–332PubMedCrossRefGoogle Scholar
  10. 10.
    Nielsen S, Smith BL, Christensen EI, Agre P (1993) Distribution of the aquaporin CHIP in secretory and resorptive epithelia and capillary endothelia. Proc Natl Acad Sci USA 90: 7275–7279PubMedCrossRefGoogle Scholar
  11. 11.
    Pappenheimer J, Heisey S, Jordan E, Downer J (1962) Perfusion of the cerebral ventricular system in unanesthetized goats. Am J Physiol 203: 763–774Google Scholar
  12. 12.
    Segal M, Pollay M (1977) The secretion of cerebrospin al fluid. Exp Eye Res 25: 127–148PubMedCrossRefGoogle Scholar
  13. 13.
    Verkman AS (2002) Physiological importance of aquaporin water channels. Ann Med 34: 192–200PubMedGoogle Scholar
  14. 14.
    Wright EM, Weidner G, Rumrich G (1977) Fluid secretion by the frog choroid plexus. Exp Eye Res 25: 149–155PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 2003

Authors and Affiliations

  • K. Oshio
    • 1
  • Y. Song
    • 2
  • A. S. Verkman
    • 2
  • Geoffrey T. Manley
    • 1
    Email author
  1. 1.Department of Neurological SurgeryUniversity of CaliforniaSan FranciscoUSA
  2. 2.Department of MedicineUniversity of CaliforniaSan FranciscoUSA

Personalised recommendations