title: Immunohistochemistry of cerebellar seizures: mossy fiber afferents play an important role in seizure spread and initiation in the rat.
abstract: 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 1.5h in every lobule. Maximum c-fos expression was seen at 3h. 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.
authors.affiliation: Department of Neurosurgery, Faculty of Medicine, University of Pécs, Pécs, Hungary.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Tóth
authors.affiliation: Department of Anatomy, Faculty of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: Gergely
authors.initials: G
authors.lastname: Molnár
authors.affiliation: Department of Anatomy, Faculty of Medicine, University of Szeged, Szeged, Hungary. Electronic address: mihaly.andras@med.u-szeged.hu.
authors.forename: András
authors.initials: A
authors.lastname: Mihály
authors.affiliation: Department of Anatomy, Faculty of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: Beáta
authors.initials: B
authors.lastname: Krisztin-Péva
authors.affiliation: Department of Anatomy, Faculty of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: Marietta
authors.initials: M
authors.lastname: Morvai
authors.affiliation: Department of Neurosurgery, Faculty of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Kopniczky
mesh_terms: D015761:4-Aminopyridine / Q000009:adverse effects* / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D007150:Immunohistochemistry; D008297:Male; D009412:Nerve Fibers / Q000378:metabolism / Q000473:pathology; D026902:Potassium Channel Blockers / Q000009:adverse effects* / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology
chemical_list: D026902:Potassium Channel Blockers; D016760:Proto-Oncogene Proteins c-fos; D015761:4-Aminopyridine
keywords: Cerebellar cortex; Epilepsy; Immunohistochemistry; Middle cerebellar peduncle; Rat.; c-fos