Status epilepticus triggers early mitochondrial fusion in the rat hippocampus in a lithium-pilocarpine model
| Autor: | Rosalinda Guevara-Guzmán, Octavio Fabián Mercado-Gómez, Luis Felipe Jiménez-García, Jael Solís-Navarrete, Laura Córdova-Dávalos, Lourdes Teresa Agredano-Moreno, Virginia Arriaga-Ávila, Dulce Carrera-Calvo |
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| Rok vydání: | 2016 |
| Předmět: |
Dynamins
Male 0301 basic medicine FIS1 endocrine system Mitochondrial DNA Time Factors Blotting Western Lithium Biology Mitochondrion Hippocampus Mitochondrial Dynamics GTP Phosphohydrolases Mitochondrial Proteins 03 medical and health sciences Status Epilepticus 0302 clinical medicine Microscopy Electron Transmission Animals MFN1 RNA Messenger Rats Wistar Inner mitochondrial membrane Pilocarpine Membrane Proteins Molecular biology Fusion protein Mitochondria Rats 030104 developmental biology Neurology mitochondrial fusion Models Animal Mitochondrial fission Neurology (clinical) Injections Intraperitoneal 030217 neurology & neurosurgery |
| Zdroj: | Epilepsy Research. 123:11-19 |
| ISSN: | 0920-1211 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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