Abstract
Using organotypic slice cultures, mechanisms for the glial cell activation during neuronal or tissue injury were investigated. Cortico-striatal slice cultures were prepared from postnatal day 2-3 Wistar/ST rats and cultured for 10-11 days. NMDA treatment (50 μM, 3h), which led to severe neuronal damages, induced MCP-1 production in astrocytes. MEK inhibitor U0126 and JNK inhibitor SP600125 significantly inhibited NMDA-induced MCP-1 production without affecting the NMDA-induced neuronal injury. On the other hand, p38 MAP kinase inhibitor SB203580 did not have any significant effects on NMDA-induced MCP-1 production. Immunostaining revealed that transient ERK phosphorylation was observed in neurons at early phase of the NMDA treatment, followed by the long-lasting ERK phosphorylation in astrocytes starting from 30 min after the administration of NMDA treatment. The delayed application of U0126 even at 3h after the end of NMDA treatment significantly suppressed MCP-1 production. These results suggest that NMDA-evoked neuronal injury induces MCP-1 production via the long-lasting activation of a MEK-ERK cascade in astrocytes. Next we examined the mechanism for the activation of microglial cells by acute tissue injury. Hippocampal slice cultures were prepared from Iba I-EGFP mice (postnatal day 6-7) and cultured for 10-11 days. Following tissue injury, microglia extended their processes toward the sites of tissue damage. This extension was significantly suppressed by apyrase, a hydrolyzing enzyme for ATP/ADP, suggesting the involvement of purinergic receptors. [J Physiol Sci. 2007;57 Suppl:S9]
