Increased GABA(A)-receptor alpha1-subunit expression in hippocampal dentate gyrus after early-life status epilepticus.
OBJECTIVE
Previous studies in neonatal (postnatal day 10) and adult rats suggest that status epilepticus (SE) induces changes in the alpha1 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.
Raol
Yogendrasinh H
YH
Division of Neurology, Pediatric Regional Epilepsy Program, Children's Hospital of Philadelphia, Philapelphia, Pennsylvania, USA.
Zhang
Guojun
G
Lund
Ingrid V
IV
Porter
Brenda E
BE
Maronski
Margaret A
MA
Brooks-Kayal
Amy R
AR
D000818:Animals; D000831:Animals, Newborn; D018891:Dentate Gyrus / Q000187:drug effects / Q000378:metabolism*; D015870:Gene Expression; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007608:Kainic Acid / Q000494:pharmacology; D008094:Lithium / Q000494:pharmacology; D021141:Nucleic Acid Amplification Techniques; D010862:Pilocarpine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000235:genetics* / Q000378:metabolism; D013226:Status Epilepticus / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism*
D011963:Receptors, GABA-A; D010862:Pilocarpine; D008094:Lithium; D007608:Kainic Acid