Effects of status epilepticus on hippocampal GABAA receptors are age-dependent.
Long-term GABA(A) receptor alterations occur in hippocampal dentate granule neurons of rats that develop epilepsy after status epilepticus in adulthood. Hippocampal GABA(A) receptor expression undergoes marked reorganization during the postnatal period, however, and the effects of neonatal status epilepticus on subsequent GABA(A) receptor development are unknown. In the current study, we utilize single cell electrophysiology and antisense mRNA amplification to determine the effect of status-epilepticus induced by lithium-pilocarpine in postnatal day 10 rat pups on GABA(A) receptor subunit expression and function in hippocampal dentate granule neurons. We find that rats subjected to lithium-pilocarpine-induced status epilepticus at postnatal day 10 show long-term GABA(A) receptor changes including a two-fold increase in alpha1 subunit expression (compared with lithium-injected controls) and enhanced type I benzodiazepine augmentation that are opposite of those seen after status epilepticus in adulthood and may serve to enhance dentate gyrus inhibition. Further, unlike adult rats, postnatal day 10 rats subjected to status epilepticus do not become epileptic. These findings suggest age-dependent differences in the effects of status epilepticus on hippocampal GABA(A) receptors that could contribute to the selective resistance of the immature brain to epileptogenesis.
Zhang
G
G
Division of Neurology, Pediatric Regional Epilepsy Program, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Raol
Y H
YH
Hsu
F-C
FC
Coulter
D A
DA
Brooks-Kayal
A R
AR
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D015152:Blotting, Northern / Q000379:methods; D002470:Cell Survival / Q000187:drug effects; D002540:Cerebral Cortex / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004569:Electroencephalography / Q000379:methods; D018755:GABA Agonists / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D018021:Lithium Chloride / Q000494:pharmacology; D018408:Patch-Clamp Techniques / Q000379:methods; D010862:Pilocarpine / Q000031:analogs & derivatives*; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013226:Status Epilepticus / Q000139:chemically induced / Q000378:metabolism*; D014741:Video Recording / Q000379:methods; D000077334:Zolpidem
D018755:GABA Agonists; D011725:Pyridines; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D010862:Pilocarpine; D000077334:Zolpidem; C029118:pilocarpic acid; D018021:Lithium Chloride