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Mislocalization of AQP4 precedes chronic seizures in the kainate model of temporal lobe epilepsy.

Abstract
It has been suggested that loss of the astrocytic water channel aquaporin-4 (AQP4) from perivascular endfeet in sclerotic hippocampi contributes to increased seizure propensity in human mesial temporal lobe epilepsy (MTLE). Whether this loss occurs prior to or as a consequence of epilepsy development remains to be resolved. In the present study, we investigated whether the expression and distribution of AQP4 was altered prior to (i.e., in the latent phase) or after the onset of chronic epileptic seizures (i.e., in the chronic phase) in the kainate (KA) model of MTLE. Immunogold electron microscopic analysis revealed that AQP4 density in adluminal endfoot membranes was reduced in KA treated rats already in the latent phase, while the AQP4 density in the abluminal endfoot membrane was stable or slightly increased. The decrease in adluminal AQP4 immunogold labeling was accompanied by a reduction in the density of AQP4's anchoring protein alpha-syntrophin. The latent and chronic phases were associated with an upregulation of the M1 isoform of AQP4, as judged by semi-quantitative Western blot analysis. Taken together, the findings in this model suggest that a mislocalization of AQP4--reflecting a loss of astrocyte polarization--is an integral part of the epileptogenic process.
AuthorsSilje Alvestad, Janniche Hammer, Eystein Hellstrøm Hoddevik, Øivind Skare, Ursula Sonnewald, Mahmood Amiry-Moghaddam, Ole Petter Ottersen
JournalEpilepsy research (Epilepsy Res) Vol. 105 Issue 1-2 Pg. 30-41 (Jul 2013) ISSN: 1872-6844 [Electronic] Netherlands
PMID23357720 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2013 Elsevier B.V. All rights reserved.
Chemical References
  • Aqp4 protein, rat
  • Aquaporin 4
  • Kainic Acid
Topics
  • Animals
  • Aquaporin 4 (metabolism)
  • Astrocytes (chemistry, drug effects, metabolism)
  • Cell Polarity (drug effects, physiology)
  • Chronic Disease
  • Disease Models, Animal
  • Epilepsy, Temporal Lobe (chemically induced, metabolism)
  • Kainic Acid (toxicity)
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Seizures (chemically induced, metabolism)

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