title: Status epilepticus triggers early mitochondrial fusion in the rat hippocampus in a lithium-pilocarpine model.
abstract: Many reports investigating the hippocampus have demonstrated an increase in neuronal damage, cellular loss, oxidative stress and mitochondrial DNA damage during status epilepticus (SE); however, information regarding alterations in mitochondrial fission and fusion events in SE is lacking. The aim of the present study was to examine the possible imbalance between mitochondrial fission and fusion in the hippocampus of male rats after acute seizure mediated by SE. In this study, we used ninety animals were randomly divided into control and SE groups and subjected to the lithium-pilocarpine model of epilepsy. Hippocampi were obtained at 3, 24 and 72h after SE, and the cytoplasmic and mitochondrial fractions of the cells were used to analyze changes in the Drp1 and Fis1 fission proteins and the Mfn1 and Opa1 fusion proteins by western blot analysis. Moreover, changes in the expression of fission and fusion mRNA transcripts were evaluated by real-time PCR. Mitochondrial morphology was also analyzed using standard transmission electron microscopy. Our data showed that the fission-related mRNA Drp1 was down-regulated rapidly after SE, while Fis1 did not show any significant changes in expression. Moreover, the mitochondrial fusion-associated proteins Mfn1 and Opa1 exhibited an increase in expression at 72h after SE. Electron microphotography revealed several morphological changes, such as swollen mitochondria and damage of the inner mitochondrial membrane, at 24h; at 72h elongation of some mitochondrial was also observed. Our results suggest that after the initiation of SE, the main regulator of the fission mRNA Drp1 is down-regulated, which in turn regulates mitochondrial fission and leads to an increase in the Mfn1 and Opa1 proteins to induce mitochondrial fusion, suggesting an imbalance of the fission and fusion processes.
authors.affiliation: Departamento de Fisiología, Facultad de Medicina Universidad Nacional Autónoma de México, México 04510, Distrito Federal, México.
authors.forename: Laura
authors.initials: L
authors.lastname: Córdova-Dávalos
authors.affiliation: Departamento de Fisiología, Facultad de Medicina Universidad Nacional Autónoma de México, México 04510, Distrito Federal, México.
authors.forename: Dulce
authors.initials: D
authors.lastname: Carrera-Calvo
authors.affiliation: Departamento de Fisiología, Facultad de Medicina Universidad Nacional Autónoma de México, México 04510, Distrito Federal, México.
authors.forename: Jael
authors.initials: J
authors.lastname: Solís-Navarrete
authors.affiliation: Departamento de Fisiología, Facultad de Medicina Universidad Nacional Autónoma de México, México 04510, Distrito Federal, México.
authors.forename: Octavio Fabián
authors.initials: OF
authors.lastname: Mercado-Gómez
authors.affiliation: Departamento de Fisiología, Facultad de Medicina Universidad Nacional Autónoma de México, México 04510, Distrito Federal, México.
authors.forename: Virginia
authors.initials: V
authors.lastname: Arriaga-Ávila
authors.affiliation: Departamento de Biología Celular, Facultad de Ciencias Universidad Nacional Autónoma de México, México 04510, Distrito Federal, México.
authors.forename: Lourdes Teresa
authors.initials: LT
authors.lastname: Agredano-Moreno
authors.affiliation: Departamento de Biología Celular, Facultad de Ciencias Universidad Nacional Autónoma de México, México 04510, Distrito Federal, México.
authors.forename: Luis Felipe
authors.initials: LF
authors.lastname: Jiménez-García
authors.affiliation: Departamento de Fisiología, Facultad de Medicina Universidad Nacional Autónoma de México, México 04510, Distrito Federal, México. Electronic address: rguevara@unam.mx.
authors.forename: Rosalinda
authors.initials: R
authors.lastname: Guevara-Guzmán
mesh_terms: D000818:Animals; D015153:Blotting, Western; D034281:Dynamins / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007274:Injections, Intraperitoneal; D008094:Lithium / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology*; D063154:Mitochondrial Dynamics; D024101:Mitochondrial Proteins / Q000378:metabolism; D023421:Models, Animal; D010862:Pilocarpine / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013226:Status Epilepticus / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors
chemical_list: C503403:Fis1 protein, rat; D008565:Membrane Proteins; C489709:Mfn1 protein, rat; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D010862:Pilocarpine; D008094:Lithium; D020558:GTP Phosphohydrolases; C498811:Opa1 protein, rat; C519851:Dnm1l protein, rat; D034281:Dynamins
keywords: Hippocampus; Mitochondrial fission; Mitochondrial fusion; Status epilepticus