Differential expression of activating transcription factor-2 and c-Jun in the immature and adult rat hippocampus following lithium-pilocarpine induced status epilepticus.
OBJECTIVE
Lithium-pilocarpine induced status epilepticus (LPSE) causes selective and age-dependent neuronal death, although the mechanism of maturation-related injury has not yet been clarified. The activating transcription factor-2 (ATF-2) protein is essential for the normal development of mammalian brain and is activated by c-Jun N-terminal kinase (JNK). It induces the expression of the c-jun gene and modulates the function of the c-Jun protein, a mediator of neuronal death and survival. Therefore, we investigated the expression of c-Jun and ATF-2 protein in the immature and adult rat hippocampus to understand their roles in LPSE-induced neuronal death.


METHODS
Lithium chloride was administrated to P10 and adult rats followed by pilocarpine. Neuronal injury was assessed by silver and cresyl violet staining, performed 72 hours after status epilepticus. For evaluation of the expression of ATF-2 and c-Jun by immunohistochemical method and Western blot, animals were sacrificed at 0, 4, 24, and 72 hours after the initiation of seizure.


RESULTS
Neuronal injury and expression of c-Jun were maturation-dependently increased by LPSE, whereas ATF-2 immunoreactivity decreased in the mature brain. Since both c-Jun and ATF-2 are activated by JNK, and targets and competitors in the same signal transduction cascade, we could speculate that ATF-2 may compete with c-Jun for JNK phosphorylation.


CONCLUSIONS
The results suggested a neuroprotective role of ATF-2 in this maturation-related evolution of neuronal cell death from status epilepticus.
Department of Neurology, The Catholic University of Korea, Seoul, Korea.
Si-Ryung
SR
Han
Cheolsu
C
Shin
Seongkyung
S
Park
Seonyoung
S
Rhyu
Jeongwook
J
Park
Yeong In
YI
Kim
D051698:Activating Transcription Factor 2 / Q000378:metabolism*; D000818:Animals; D018692:Antimanic Agents / Q000494:pharmacology; D015153:Blotting, Western; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007150:Immunohistochemistry; D008094:Lithium / Q000494:pharmacology; D008916:Miotics / Q000494:pharmacology; D010862:Pilocarpine / Q000494:pharmacology; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D051381:Rats; D013226:Status Epilepticus / Q000139:chemically induced*
D051698:Activating Transcription Factor 2; D018692:Antimanic Agents; D008916:Miotics; D016755:Proto-Oncogene Proteins c-jun; D010862:Pilocarpine; D008094:Lithium