PMID- 22766234 OWN - NLM STAT- MEDLINE DCOM- 20130123 LR - 20161125 IS - 1873-7544 (Electronic) IS - 0306-4522 (Linking) VI - 221 DP - 2012 Sep 27 TI - 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. PG - 12-20 LID - 10.1016/j.neuroscience.2012.06.058 [doi] AB - 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. CI - Copyright (c) 2012 IBRO. Published by Elsevier Ltd. All rights reserved. FAU - Hanaya, R AU - Hanaya R AD - Department of Neurosurgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 734-8551, Japan. hanaya@m2.kufm.kagoshima-u.ac.jp FAU - Hosoyama, H AU - Hosoyama H FAU - Sugata, S AU - Sugata S FAU - Tokudome, M AU - Tokudome M FAU - Hirano, H AU - Hirano H FAU - Tokimura, H AU - Tokimura H FAU - Kurisu, K AU - Kurisu K FAU - Serikawa, T AU - Serikawa T FAU - Sasa, M AU - Sasa M FAU - Arita, K AU - Arita K LA - eng PT - Journal Article DEP - 20120703 PL - United States TA - Neuroscience JT - Neuroscience JID - 7605074 RN - 0 (Atrn protein, mouse) RN - 0 (Membrane Glycoproteins) RN - 0 (Membrane Proteins) RN - 0 (Nerve Tissue Proteins) RN - 0 (Sv2a protein, rat) RN - 0 (Synaptotagmin I) RN - 0 (Syt1 protein, rat) RN - 0Z5B2CJX4D (Fluorodeoxyglucose F18) RN - EC 3.5.- (Amidohydrolases) RN - EC 3.5.1.15 (aspartoacylase) SB - IM MH - Amidohydrolases/genetics MH - Animals MH - Brain Mapping MH - Brain Waves/genetics MH - Cerebral Cortex/diagnostic imaging/*metabolism MH - Disease Models, Animal MH - Electroencephalography MH - Epilepsy, Absence/diagnostic imaging/genetics/*pathology MH - Female MH - Fluorodeoxyglucose F18 MH - Gene Expression Regulation/genetics MH - Hippocampus/diagnostic imaging/*metabolism MH - Male MH - Membrane Glycoproteins/*metabolism MH - Membrane Proteins/genetics MH - Mutation/genetics MH - Nerve Tissue Proteins/*metabolism MH - Positron-Emission Tomography MH - Radiography MH - Rats MH - Rats, Mutant Strains MH - Rats, Wistar MH - Seizures/complications/diagnostic imaging/genetics/*pathology MH - Synaptotagmin I/*metabolism EDAT- 2012/07/07 06:00 MHDA- 2013/01/24 06:00 CRDT- 2012/07/07 06:00 PHST- 2012/02/03 00:00 [received] PHST- 2012/06/25 00:00 [revised] PHST- 2012/06/25 00:00 [accepted] PHST- 2012/07/07 06:00 [entrez] PHST- 2012/07/07 06:00 [pubmed] PHST- 2013/01/24 06:00 [medline] AID - S0306-4522(12)00676-8 [pii] AID - 10.1016/j.neuroscience.2012.06.058 [doi] PST - ppublish SO - Neuroscience. 2012 Sep 27;221:12-20. doi: 10.1016/j.neuroscience.2012.06.058. Epub 2012 Jul 3.