A systemic administration of NMDA induces immediate early gene pip92 in the hippocampus

In the mammalian CNS, aspartate and glutamate are major excitatory amino ac ids, and their receptors are believed to mediate a wide range of physiologi cal and pathological processes, including neurotransmission, plasticity, ex citotoxicity, and Various forms of neurodegeneration. The immediate early g ene pip92 has been identified in serum-stimulated BALB/c 3T3 fibroblasts, a ctivated T lymphocytes treated with cycloheximide, and fibroblast growth fa ctor-stimulated hippocampal cells during neuronal differentiation. In this study we have demonstrated that pip92 is expressed in the mouse brain after a single intraperitoneal injection of NMDA. The distribution of pip92 mRNA levels in the NMDA-treated mouse brain was investigated using in situ RT-P CR. The region-specific activation of pip92 in the CNS was observed 3 h aft er NMDA injection, and high levels of pip92 mRNA were detected in the hippo campal dentate gyrus and piriform cortex regions. In addition, the activati on of pip92 by NMDA was mediated by activation of mitogen-activated protein kinases (MAPKs), such as c-Jun N-terminal kinase (JNK) and p38 kinase, but not extracellular signal-regulated kinase (ERK) in the mouse hippocampus a nd immortalized rat hippocampal progenitor cells. This study suggests that pip92 is likely to play an important role in neuronal cell death induced by excitotoxic NMDA injury in the CNS.