Increased GABA_A-Receptor α1-Subunit Expression in Hippocampal Dentate Gyrus after Early-life Status Epilepticus

Authors: Raol, YogendraSinh H.¹; Zhang, Guojun¹; Lund, Ingrid V.²; Porter, Brenda E.¹; Maronski, Margaret A.¹; Brooks-Kayal, Amy R.

Source: Epilepsia, Volume 47, Number 10, October 2006 , pp. 1665-1673(9)

Publisher: Wiley-Blackwell

Abstract:

Summary: 

Purpose: Previous studies in neonatal (postnatal day 10) and adult rats suggest that status epilepticus (SE) induces changes in the α1 subunit of the GABA_A receptor (GABRA1) in dentate granule neurons (DGNs) that are age dependent and vary inversely with the likelihood of epilepsy development. In the present study, we examined GABRA1 expression after SE at postnatal day 20 (P20), an intermediate age when only a subset of SE-exposed animals develop epilepsy.

Methods: SE was induced with lithium-pilocarpine or kainate at P20. Animals were video-EEG monitored after SE to determine the presence or absence of spontaneous seizures. GABRA1 mRNA and protein levels were determined 7 days or 3 months later in SE-exposed and control animals by using a combination of aRNA amplification, Western blotting, and immunohistochemistry techniques.

Results: GABRA1 mRNA levels in DGNs of SE-exposed rats that did not become epileptic were higher than those in control rats, but were not different from DGNs in epileptic SE-exposed rats. GABRA1 protein levels in dentate gyrus were significantly increased in both epileptic and nonepileptic SE-exposed rats compared with controls. GABRA1 mRNA changes were region specific and did not occur in CA1 or CA3 areas of hippocampus. GABRA1 alterations were present by 1 week after P20 SE and were similar whether pilocarpine or kainate was used to induced SE.

Conclusions: P20 SE results in persistent increases in GABRA1 levels selectively in dentate gyrus. These changes preceded the onset of epilepsy, were not model specific, and occurred in both epileptic and nonepileptic animals.

Keywords: Seizure; Epilepsy; GABAA receptor; Postnatal development; Pilocarpine; Kainate

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1528-1167.2006.00640.x

Affiliations: 1: Division of Neurology, Pediatric Regional Epilepsy Program, Children's Hospital of Philadelphia 2: Neuroscience Graduate Group

Publication date: 2006-10-01

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