ZIF268 AND FOS-LIKE IMMUNOREACTIVITY IN TETANUS TOXIN-INDUCED EPILEPSY - RECIPROCAL CHANGES IN THE EPILEPTIC FOCUS AND THE SURROUND

Altered gene expression for a number of molecules has been suggested a s one of the underlying mechanisms of epileptogenesis. Changes in expr ession of the immediate early genes, zif268 and c-fos, were investigat ed in chronic focal epilepsy induced by tetanus toxin (TT, 20-35 ng) i njected in the rat motor cortex. Most rats injected with TT and perfus ed on postoperative day 5, 7 or 14 had recurrent focal seizures after a latent period of 4-13 days, and showed enhanced Zif268 immunoreactiv ity in a cluster of neurons at the injection site, as well as reduced Zif268 immunoreactivity in a distinct cortical zone around this cluste r. C-fos or Fos-related immunoreactivity was decreased over widespread areas of frontoparietal and piriform cortex in epileptic rats, except for a focus at the injection site which, in most cases, showed increa ses in Fos-like immunoreactivity. Some epileptic rats showed increased Zif268 immunoreactivity in neurons of the ipsilateral ventral lateral and central lateral thalamic nuclei and increased Zif268 and Fos-like immunoreactivity in the pontine nuclei. Rats perfused before onset of seizures, showed no overt changes other than a slight decrease in Zif 268 and Fos-like immunoreactivity at the injection site. The reciproca l changes in Zif268 immunoreactive neurons in the epileptic focus and the immediate surround parallel changes in gene expression for a numbe r of molecules important in epileptogenesis and suggest a state of fun ctional disconnection of the epileptic focus from other cortical areas that may contribute to the development and maintenance of focal epile psy. (C) 1997 Elsevier Science B.V.