Three distinct roles of aquaporin-4 in brain function revealed by knockout mice

A. S. Verkman, Devin K. Binder, Orin Bloch, Kurtis Auguste, Marios C. Papadopoulos

Research output: Contribution to journalReview article

219 Citations (Scopus)

Abstract

Aquaporin-4 (AQP4) is expressed in astrocytes throughout the central nervous system, particularly at the blood-brain and brain-cerebrospinal fluid barriers. Phenotype analysis of transgenic mice lacking AQP4 has provided compelling evidence for involvement of AQP4 in cerebral water balance, astrocyte migration, and neural signal transduction. AQP4-null mice have reduced brain swelling and improved neurological outcome in models of (cellular) cytotoxic cerebral edema including water intoxication, focal cerebral ischemia, and bacterial meningitis. However, brain swelling and clinical outcome are worse in AQP4-null mice in models of vasogenic (fluid leak) edema including cortical freeze-injury, brain tumor, brain abscess and hydrocephalus, probably due to impaired AQP4-dependent brain water clearance. AQP4 deficiency or knock-down slows astrocyte migration in response to a chemotactic stimulus in vitro, and AQP4 deletion impairs glial scar progression following injury in vivo. AQP4-null mice also manifest reduced sound- and light-evoked potentials, and increased threshold and prolonged duration of induced seizures. Impaired K+ reuptake by astrocytes in AQP4 deficiency may account for the neural signal transduction phenotype. Based on these findings, we propose modulation of AQP4 expression or function as a novel therapeutic strategy for a variety of cerebral disorders including stroke, tumor, infection, hydrocephalus, epilepsy, and traumatic brain injury.

Original languageEnglish (US)
Pages (from-to)1085-1093
Number of pages9
JournalBiochimica et Biophysica Acta - Biomembranes
Volume1758
Issue number8
DOIs
StatePublished - Aug 1 2006
Externally publishedYes

Fingerprint

Aquaporin 4
Knockout Mice
Brain
Astrocytes
Brain Edema
Signal transduction
Hydrocephalus
Swelling
Water
Tumors
Signal Transduction
Water Intoxication
Cerebrospinal fluid
Phenotype
Brain Abscess
Bacterial Meningitides
Bioelectric potentials
Wounds and Injuries
Neurology
Brain Ischemia

Keywords

  • AQP4
  • Brain edema
  • Cell migration
  • Epilepsy
  • Transgenic mouse
  • Water transport

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Cell Biology

Cite this

Three distinct roles of aquaporin-4 in brain function revealed by knockout mice. / Verkman, A. S.; Binder, Devin K.; Bloch, Orin; Auguste, Kurtis; Papadopoulos, Marios C.

In: Biochimica et Biophysica Acta - Biomembranes, Vol. 1758, No. 8, 01.08.2006, p. 1085-1093.

Research output: Contribution to journalReview article

Verkman, A. S. ; Binder, Devin K. ; Bloch, Orin ; Auguste, Kurtis ; Papadopoulos, Marios C. / Three distinct roles of aquaporin-4 in brain function revealed by knockout mice. In: Biochimica et Biophysica Acta - Biomembranes. 2006 ; Vol. 1758, No. 8. pp. 1085-1093.
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