HYPOGLYCEMIA-ELICITED IMMEDIATE-EARLY GENE-EXPRESSION IN NEURONS AND GLIA OF THE HIPPOCAMPUS - NOVEL PATTERNS OF FOS, JUN, AND KROX EXPRESSION FOLLOWING EXCITOTOXIC INJURY

In the hippocampus there is a graded vulnerability of neuronal subpopu lations to hypoglycemia-induced degeneration, most likely due to excit otoxic activation of glutamate receptors. The present study was conduc ted to investigate whether the induction of transcription factors of t he immediate early gene (IEG) family after hypoglycemia reflects these different grades of neuronal vulnerability. We studied the expression profile of seven IEG-coded proteins in the rat hippocampus following severe insulin-induced hypoglycemia with 30 min of EEG isoelectricity and various survival periods for up to 42 h after glucose replenishmen t. Immunocytochemistry was performed on vibratome sections with specif ic poly clonal antisera directed against c-FOS, FOS B, c-JUN, JUN B, J UN D, KROX-24, acid KROX-20. To unequivocally define the type of glial cells showing IEG induction, we investigated coexpression of c-FOS an d glial marker proteins (glial fibrillary acid protein [GFAP], OX-42) by confocal laser scanning microscopy, Up to 3 h after glucose repleni shment, differential temporospatial induction of IEG-coded transcripti on factors of the FOS, JUN and KROX families were observed in moderate ly injured neuronal subpopulations, including the majority of dentate granule cells and CA3 neurons. At later time points, however, a delaye d and persistent c-JUN expression was found in severely, but reversibl y, injured CA1 neurons and in neurons in the immediate vicinity of irr eversibly damaged neurons in the crest of the dentate gyrus. Similar t o the results with experimental models of central and peripheral axoto my, selective c-JUN induction in these neurons may represent an initia l event in the regeneration process of sublethally injured neurons. In contrast to other models of excitotoxic injury such as ischemia and e pilepsy, marked glial c-FOS expression was restricted to astrocytes, a s assessed by confocal laser scanning microscopy.