KAINIC ACID-INDUCED EXCITOTOXICITY IS ASSOCIATED WITH A COMPLEX C-FOSAND C-JUN RESPONSE WHICH DOES NOT PRECLUDE EITHER CELL-DEATH OR SURVIVAL

c-fos and c-jun mRNA induction and c-Pos and c-Jun protein expression were examined in the brains of adult rats subjected to systemic kainic acid (KA) injection at convulsant doses. Induction of c-fos and c-jun mRNA, as seen with in situ hybridization, occurred in the piriform an d entorhinal cortices, neocortex, amygdala, hippocampus, dentate gyrus , and discrete thalamic nuclei. This was followed by c-Fos protein exp ression, as revealed with immunohistochemistry, in the same regions. H owever, the distribution of c-Jun protein expression differed dependin g on the antibody used. The distribution of cells immunostained with t he antibody c-Jun (AB-I) was similar to that of c-jun mRNA, but the di stribution of cells immunostained with the antibody c-Jun/AP1 (N) was restricted to a few neurons in the pyramidal cell layer of CA1 and CA3 , layer II of the piriform and entorhinal cortices, basal amygdala, an d discrete thalamic nuclei. Although the regional distribution of c-Fo s-and c-Jun-immunoreactive cells in the hippocampus, layer II of the e ntorhinal and piriform cortices, basal amygdala, and discrete thalamic nuclei matched the distribution of cells committed to dying, c-Fos-an d c-Jun-immunoreactive cells in the neocortex and dentate gyrus surviv ed. Therefore, the present data show that c-fos and c-jun are not pred ictors of either cell death or survival, but rather, markers of cells sensitive to KA excitotoxicity. Western blots to c-Fos showed a double band at p62 in samples containing the hippocampus and entorhinal and piriform cortices (hip samples) and in samples containing the neocorte x (cortex samples). The upper band was abolished following preincubati on of the samples with alkaline phosphatase, thus suggesting c-Fos pho sphorylation. Western blots to c-Jun (AB-1) showed a single band at ab out p39 in hip and cortex. However, Western blots to c-Jun/AP1 (N) ide ntified two bands. One band at about p39 was seen in control rats and the cortex of KA-treated rats. Another band at p26 was observed only i n hip samples of KA-treated rats. In addition, decreased c-Jun N-termi nal kinase 1 (JNK-1) expression, as revealed on Western blots, was coi ncidental with the appearance of the p26 c-Jun-immunoreactive band in KA-treated rats. These results show that c-Fos and different Jun-relat ed antigens are expressed following KA excitotoxicity, and that posttr anslational modifications involving phosphorylation of c-Fos and Jun(s ) may occur following KA injection. These results also stress the nece ssity of examining the composition of Fos and Jun-related antigens and the metabolic state of Fos and Jun(s) in different experimental model s of nervous system injury. (C) 1997 John Wiley & Sons, Inc. J Neurobi ol.