JUN, FOS, KROX, AND CREB TRANSCRIPTION FACTOR PROTEINS IN THE RAT CORTEX - BASAL EXPRESSION AND INDUCTION BY SPREADING DEPRESSION AND EPILEPTIC SEIZURES

The expression of the nuclear c-JUN, JUN B, JUN D, c-FOS, FOS B, KROX- 24, and CREB transcription factors was investigated in the cortex of a dult rats by immunocytochemistry. The expression patterns were studied in untreated rats and up to 24 hours following topical application of 1 M KCl to the cortical surface (KCl) or i.v. injection of bicucullin e (BIC). Topical KCl induced cortical spreading depression and systemi c injection of bicuculline evoked generalized tonic-clonic seizures. I n untreated rats, JUN B, c-FOS, and FOS B were expressed in a small nu mber of neurons in the piriform, perirhinal, entorhinal, and insular c ortex and in layers II, III, and VI of all neocortical areas. In contr ast, c-JUN, JUN D, and KROX-24 were expressed in all cortical layers b ut with different intensities of immunoreactivity (IR): c-JUN-IR was g enerally weak and predominantly present in layers II, III, and VI. JUN D-IR was equally strong in all layers. KROX-24 showed a prominent exp ression in layers II, IV, and VI. The CREB protein exhibited a high an d fairly homogeneous constitutive expression throughout the cortex wit h a slight preponderance in layer II and piriform cortex. Following KC l or BIC, a strong induction was seen for c-FOS, JUN B, and KROX-24, w hereas c-JUN, JUN D, and FOS B showed only a moderate increase compare d to basal levels. Changes of CREB-IR could not be detected. The local ization of induced JUN, FOS, and KROX proteins reflected the pattern o f labelling in untreated animals but demonstrated a higher intensity o f labelling and an increased number of immunoreactive nuclei. The inte nsity and persistence of IR as well as the number of labelled cells fo llowing BIC exceeded those following KCl. Following BIC, increased lev els of FOS B and JUN D were still present after 24 hours. Counterstain ing with cresyl-violet and GFAP, a marker for astrocytes, revealed tha t JUN, FOS, and KROX proteins were expressed in neurons but not in gli al cell populations. The present data demonstrate that CREB, JUN, FOS, and KROX transcription factors exhibit a layer-specific expression in the cerebral cortex with only slight area-specific differences both i n untreated rats and following stimulation with KCl and BIC. The expre ssion of transcription factor proteins indicate complex molecular gene tic changes in cortical neurons due to pathophysiological events such as seizure activity and spreading depression.