title: Low distribution of synaptic vesicle protein 2A and synaptotagimin-1 in the cerebral cortex and hippocampus of spontaneously epileptic rats exhibiting both tonic convulsion and absence seizure.
abstract: The spontaneously epileptic rat (SER) is a double mutant (zi/zi, tm/tm) which begins to exhibit tonic convulsions and absence seizures after 6 weeks of age, and repetitive tonic seizures over time induce sclerosis-like changes in SER hippocampus with high brain-derived neurotrophic factor (BDNF) expression. Levetiracetam, which binds to synaptic vesicle protein 2A (SV2A), inhibited both tonic convulsions and absence seizures in SERs. We studied SER brains histologically and immunohistochemically after verification by electroencephalography (EEG), as SERs exhibit seizure-related alterations in the cerebral cortex and hippocampus. SERs did not show interictal abnormal spikes and slow waves typical of focal epilepsy or symptomatic generalized epilepsy. The difference in neuronal density of the cerebral cortex was insignificant between SER and Wistar rats, and apoptotic neurons did not appear in SERs. BDNF distributions portrayed higher values in the entorhinal and piriform cortices which would relate with hippocampal sclerosis-like changes. Similar synaptophysin expression in the cerebral cortex and hippocampus was found in both animals. Low and diffuse SV2A distribution portrayed in the cerebral cortex and hippocampus of SERs was significantly less than that of all cerebral lobes and inner molecular layer (IML) of the dentate gyrus (DG) of Wistar rats. The extent of low SV2A expression/distribution in SERs was particularly remarkable in the frontal (51% of control) and entorhinal cortices (47%). Lower synaptotagmin-1 expression (vs Wistar rats) was located in the frontal (31%), piriform (13%) and entorhinal (39%) cortices, and IML of the DG (38%) in SER. Focal low distribution of synaptotagmin-1 accompanying low SV2A expression may contribute to epileptogenesis and seizure propagation in SER.
authors: Department of Neurosurgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 734-8551, Japan. hanaya@m2.kufm.kagoshima-u.ac.jp
authors: R
authors: R
authors: Hanaya
authors: H
authors: H
authors: Hosoyama
authors: S
authors: S
authors: Sugata
authors: M
authors: M
authors: Tokudome
authors: H
authors: H
authors: Hirano
authors: H
authors: H
authors: Tokimura
authors: K
authors: K
authors: Kurisu
authors: T
authors: T
authors: Serikawa
authors: M
authors: M
authors: Sasa
authors: K
authors: K
authors: Arita
mesh_terms: D000581:Amidohydrolases / Q000235:genetics; D000818:Animals; D001931:Brain Mapping; D058256:Brain Waves / Q000235:genetics; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000378:metabolism*; D004195:Disease Models, Animal; D004569:Electroencephalography; D004832:Epilepsy, Absence / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology*; D005260:Female; D019788:Fluorodeoxyglucose F18; D005786:Gene Expression Regulation / Q000235:genetics; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D049268:Positron-Emission Tomography; D011859:Radiography; D051381:Rats; D011922:Rats, Mutant Strains; D017208:Rats, Wistar; D012640:Seizures / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology*; D050863:Synaptotagmin I / Q000378:metabolism*
chemical_list: C117928:Atrn protein, mouse; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C489618:Sv2a protein, rat; D050863:Synaptotagmin I; C494312:Syt1 protein, rat; D019788:Fluorodeoxyglucose F18; D000581:Amidohydrolases; C019751:aspartoacylase