Differential Expression of Activating Transcription Factor-2 and c-Jun in the Immature and Adult Rat Hippocampus Following Lithium-Pilocarpine Induced Status Epilepticus

다국어 초록 (Multilingual Abstract)

Purpose: 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. Materials and 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. Conclusion: The results
suggested a neuroprotective role of ATF-2 in this maturation-related evolution of neuronal cell death from status epilepticus.

다국어 초록 (Multilingual Abstract)

Purpose: 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. Materials and 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. Conclusion: The results
suggested a neuroprotective role of ATF-2 in this maturation-related evolution of neuronal cell death from status epilepticus.

참고문헌 (Reference)

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