SOMAN-INDUCED SEIZURES RAPIDLY ACTIVATE ASTROCYTES AND MICROGLIA IN DISCRETE BRAIN-REGIONS

Neurons in the piriform cortex and the pontine nucleus locus coeruleus express elevated levels of the immediate early gene protein product, Fos, within 30-45 minutes of a seizurogenic dose of the anticholineste rase, soman (Zimmer et al., [1997] J. Comp. Neurol. 378:468-481). By 2 4 hours following soman injection, there is marked neuropathology in t he piriform cortex. These findings suggest selective, regional vulnera bility in response to the seizurogenic actions of soman. In the presen t study, we determined that soman-induced seizures also cause selectiv e, rapid activation of astrocytes and microglia in the piriform cortex and other brain regions. Animals were killed at different intervals b etween 1 hour and 24 hours after a convulsive dose of soman. Brain sec tions were processed for immunocytochemical detection of astrocytes wi th antibodies against glial fibrillary acidic protein, and microglia a nd macrophages with antibodies against the complement receptor 3 prote in, OX-42. The results demonstrate that following soman administration : (1) there is a rapid increase in glial fibrillary acidic protein sta ining in astrocytes of the piriform cortex (1 hour); (ii) reactive ast rocytes are specifically restricted to layer II and the superficial bo undaries of layer III of the piriform cortex. These are the same layer s in which neurons express Fos within 30-45 minutes following soman ad ministration; (3) between 1 and 4 hours, resting (ramified) microglia in the piriform cortex and the hippocampus alter their morphology to r esemble active microglia. From 4-8 hours, active microglia undergo mor phological changes characteristic of reactive microglia that resemble macrophages. Taken together, these observations indicate that astrocyt es and microglia in brain regions susceptible to soman become rapidly ''reactive'' in response to seizures. The highly specific anatomical c odistribution of reactive glia and Fos-expressing neurons suggests tha t intensely active neurons provide local signals that trigger reactive changes in neighboring glia. (C) 1997 Wiley-Liss, Inc.