Alteration of Gene Associated with Retinoid-interferon-induced Mortality-19-expressing Cell Types in the Mouse...

The gene associated with retinoid-interferon-induced mortality-19 (GRIM-19) plays several significant roles in cellular processes, including ATP synthesis, reactive oxygen species formation, and the regulation of glycolytic enzyme activity, which are closely related to the pathophysiological mechanisms of epilepsy. Therefore, we investigated the expression pattern of GRIM-19 in the CA1 area of the hippocampus in 8-week-old male C57BL/6 mice following pilocarpine-induced status epilepticus (SE). Neuronal death in the hippocampal CA1 area was prominently observed at 4 and 7 days after SE, and astrocytes and microglia became progressively activated beginning at 1 day after SE. GRIM-19 immunoreactivity was decreased in the damaged pyramidal cell layer but markedly increased in the stratum radiatum and stratum lacunosum-moleculare of the hippocampus at 4 and 7 days after SE. In addition, the cell types of GRIM-19-expressing cells in the epileptic hippocampus were identified. GRIM-19 was mainly co-localized in neurons but only slightly expressed in glia in the normal hippocampus. Most of the GRIM-19-positive cells induced by SE in the stratum radiatum and stratum lacunosum-moleculare were glial fibrillary acidic protein-expressing reactive astrocytes. Moreover, we observed that both GRIM-19 and pyruvate kinase isozyme M2, a glycolytic enzyme, were highly expressed in reactive astrocytes after SE. These results indicate that expression of GRIM-19 in the hippocampus is mainly observed in neurons under normal conditions but is altered in the SE mouse model as evidenced by its increased expression in reactive astrocytes. The possible role of GRIM-19 in the glycolytic activity of reactive astrocytes is also discussed.