Disruption of dystroglycan-laminin interactions modulates water uptake by astrocytes

Brian T. Hawkins, Yu Huan Gu, Yoshikane Izawa, Gregory J. Del Zoppo

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Cerebral edema is a serious complication of ischemic brain injury. Cerebral edema includes accumulation of extracellular fluid due to leakage of the brain's microvessel permeability barrier, and swelling of astrocytes as they absorb water from the extracellular space. Expression of matrix adhesion receptors in brain microvessels decreases in ischemic stroke; this contributes to increased microvessel permeability and detachment of astrocytes from the extracellular matrix (ECM). Since loss of the astrocyte adhesion receptor dystroglycan has been associated with disrupted polarization of ion and water channels, we hypothesized that adhesion of astrocytes to the ECM contributes to regulation of water uptake, and that disruption of matrix adhesion impairs the ability of astrocytes to direct water transport. To test this hypothesis, the capacity of astrocytes to take up water was measured using a fluorescence self-quenching assay under both oxygen/glucose deprivation (OGD) and direct antibody-mediated blockade of α-dystroglycan. Both conditions decreased the rate of water uptake. Moreover, inhibiting proteolytic cleavage of dystroglycan that occurs in OGD abrogated the effect of OGD, but not direct blockade of α-dystroglycan, indicating that interfering with dystroglycan-matrix binding itself affects water uptake. Activation of extracellular signal-related kinase (ERK) by OGD was dependent on α-dystroglycan binding, and inhibition of ERK activity with U0126 abrogated the loss of water uptake following OGD. These studies demonstrate for the first time that water uptake in astrocytes is regulated by dystroglycan-dependent signaling associated with matrix adhesion. This presents a novel potential approach to the treatment of cerebral edema.

Original languageEnglish
Pages (from-to)89-96
Number of pages8
JournalBrain Research
Volume1503
DOIs
Publication statusPublished - 2013 Mar 29
Externally publishedYes

Fingerprint

Dystroglycans
Laminin
Astrocytes
Water
Oxygen
Brain Edema
Glucose
Microvessels
Extracellular Matrix
Permeability
Phosphotransferases
Aquaporins
Extracellular Fluid
Brain
Extracellular Space
Ion Channels
Brain Injuries
Fluorescence
Stroke
Antibodies

Keywords

  • Adhesion
  • Astrocyte
  • Dystroglycan
  • Edema
  • Extracellular matrix
  • Homeostasis
  • Ischemia
  • Oxygen/glucose deprivation
  • Water transport

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Developmental Biology
  • Molecular Biology

Cite this

Disruption of dystroglycan-laminin interactions modulates water uptake by astrocytes. / Hawkins, Brian T.; Gu, Yu Huan; Izawa, Yoshikane; Del Zoppo, Gregory J.

In: Brain Research, Vol. 1503, 29.03.2013, p. 89-96.

Research output: Contribution to journalArticle

Hawkins, Brian T. ; Gu, Yu Huan ; Izawa, Yoshikane ; Del Zoppo, Gregory J. / Disruption of dystroglycan-laminin interactions modulates water uptake by astrocytes. In: Brain Research. 2013 ; Vol. 1503. pp. 89-96.
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