Immunohistochemistry of cerebellar seizures: Mossy fiber afferents play an important role in seizure spread and initiation in the rat

Zoltán Tóth, Gergely Molnár, András Mihály, Beáta Krisztin-Péva, Marietta Morvai, Zsolt Kopniczky

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Clinical reports suggest the participation of the cerebellum in epilepsy. Mossy fibers are the main excitatory afferents of the cerebellar cortex; most of them use glutamate and strongly excite granule cells through NMDA and AMPA receptors. The role of the ponto-cerebellar mossy fibers in cerebellar neuronal hyperactivity was investigated in the present study in experimental adult Wistar rats. We detected neuronal hyperactivity through the expression of the glutamate-induced c-fos protein, by means of immunohistochemistry and immunoblotting in the vermis and in the hemispheres. Generalized seizures were induced by means of intraperitoneal 4-aminopyridine injections. Following the 4-aminopyridine seizures, the c-fos expression of cerebellar granule cells was significantly elevated at 1.5. h in every lobule. Maximum c-fos expression was seen at 3. h. The role of the ponto-cerebellar mossy fiber afferents in the induction of c-fos expression was examined after the transection of the middle cerebellar peduncle on the left side. Immunohistochemical analysis 14 days after the surgery revealed that the synapsin I immunoreactivity was significantly reduced in the cerebellar cortex on the operated side, compared to the sham-operated controls and to the non-operated cerebellar hemisphere of the operated animals, indicating the degeneration of mossy fiber terminals. Transection of the middle cerebellar peduncle suppressed cerebellar c-fos expression in the vermis and in the hemispheres significantly. These findings suggest the strong involvement of the middle cerebellar peduncle and the ponto-cerebellar mossy fibers in the pathophysiology of cerebellar epilepsy.

Original languageEnglish
Pages (from-to)47-55
Number of pages9
JournalActa histochemica
Issue number1
Publication statusPublished - jan. 1 2015


ASJC Scopus subject areas

  • Histology
  • Cell Biology

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