RGD Reference Report - Decreased expression of the glial water channel aquaporin-4 in the intrahippocampal kainic acid model of epileptogenesis. - Rat Genome Database

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Decreased expression of the glial water channel aquaporin-4 in the intrahippocampal kainic acid model of epileptogenesis.

Authors: Lee, DJ  Hsu, MS  Seldin, MM  Arellano, JL  Binder, DK 
Citation: Lee DJ, etal., Exp Neurol. 2012 May;235(1):246-55. doi: 10.1016/j.expneurol.2012.02.002. Epub 2012 Feb 14.
RGD ID: 8695999
Pubmed: PMID:22361023   (View Abstract at PubMed)
PMCID: PMC3334411   (View Article at PubMed Central)
DOI: DOI:10.1016/j.expneurol.2012.02.002   (Journal Full-text)

Recent evidence suggests that astrocytes may be a potential new target for the treatment of epilepsy. The glial water channel aquaporin-4 (AQP4) is expressed in astrocytes, and along with the inwardly-rectifying K(+) channel K(ir)4.1 is thought to underlie the reuptake of H(2)O and K(+) into glial cells during neural activity. Previous studies have demonstrated increased seizure duration and slowed potassium kinetics in AQP4(-/-) mice, and redistribution of AQP4 in hippocampal specimens from patients with chronic epilepsy. However, the regulation and role of AQP4 during epileptogenesis remain to be defined. In this study, we examined the expression of AQP4 and other glial molecules (GFAP, K(ir)4.1, glutamine synthetase) in the intrahippocampal kainic acid (KA) model of epilepsy and compared behavioral and histologic outcomes in wild-type mice vs. AQP4(-/-) mice. Marked and prolonged reduction in AQP4 immunoreactivity on both astrocytic fine processes and endfeet was observed following KA status epilepticus in multiple hippocampal layers. In addition, AQP4(-/-) mice had more spontaneous recurrent seizures than wild-type mice during the first week after KA SE as assessed by chronic video-EEG monitoring and blinded EEG analysis. While both genotypes exhibited similar reactive astrocytic changes, granule cell dispersion and CA1 pyramidal neuron loss, there were an increased number of fluorojade-positive cells early after KA SE in AQP4(-/-) mice. These results indicate a marked reduction of AQP4 following KA SE and suggest that dysregulation of water and potassium homeostasis occurs during early epileptogenesis. Restoration of astrocytic water and ion homeostasis may represent a novel therapeutic strategy.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
status epilepticus severityISOAqp4 (Mus musculus)8695999; 8695999 RGD 
status epilepticus  ISOAqp4 (Mus musculus)8695999; 8695999 RGD 
status epilepticus severityIMP 8695999 RGD 
status epilepticus  IEP 8695999 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Aqp4  (aquaporin 4)

Genes (Mus musculus)
Aqp4  (aquaporin 4)

Genes (Homo sapiens)
AQP4  (aquaporin 4)


Additional Information