Status epilepticus triggers early mitochondrial fusion in the rat hippocampus in a lithium-pilocarpine model
Por:
Laura, Cordova-Davalos, Dulce, Carrera-Calvo, Jael, Solis-Navarrete, Octavio Fabian, Mercado-Gomez, Virginia, Arriaga-Avila, Lourdes Teresa, Agredano-Moreno, Luis Felipe, Jimenez-Garcia, Rosalinda, Guevara-Guzman
Publicada:
1 jul 2016
Resumen:
Many reports investigating the hippocampus have demonstrated an increase
in neuronal damage, cellular loss, oxidative stress and mitochondria!
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 72 h 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 Opal 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 72 h after SE. Electron microphotography revealed several
morphological changes, such as swollen mitochondria and damage of the
inner mitochondrial membrane, at 24 h; at 72 h 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. (C)
2016 Elsevier B.V. All rights reserved.
Filiaciones:
Laura, Cordova-Davalos:
Univ Nacl Autonoma Mexico, Fac Med, Dept Fisiol, Apartado Postal 70250, Mexico City 04510, DF, Mexico
Dulce, Carrera-Calvo:
Univ Nacl Autonoma Mexico, Fac Med, Dept Fisiol, Apartado Postal 70250, Mexico City 04510, DF, Mexico
Jael, Solis-Navarrete:
Univ Nacl Autonoma Mexico, Fac Med, Dept Fisiol, Apartado Postal 70250, Mexico City 04510, DF, Mexico
Octavio Fabian, Mercado-Gomez:
Univ Nacl Autonoma Mexico, Fac Med, Dept Fisiol, Apartado Postal 70250, Mexico City 04510, DF, Mexico
Virginia, Arriaga-Avila:
Univ Nacl Autonoma Mexico, Fac Med, Dept Fisiol, Apartado Postal 70250, Mexico City 04510, DF, Mexico
Lourdes Teresa, Agredano-Moreno:
Univ Nacl Autonoma Mexico, Fac Ciencias, Dept Biol Celular, Mexico City 04510, DF, Mexico
Luis Felipe, Jimenez-Garcia:
Univ Nacl Autonoma Mexico, Fac Ciencias, Dept Biol Celular, Mexico City 04510, DF, Mexico
Rosalinda, Guevara-Guzman:
Univ Nacl Autonoma Mexico, Fac Med, Dept Fisiol, Apartado Postal 70250, Mexico City 04510, DF, Mexico
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