Energetic, oxidative and ionic exchange in rat brain and liver mitochondria at experimental audiogenic epilepsy (Krushinsky–Molodkina model)

Венедиктова, Н. И.; Горбачева, О. С.; Belosludtseva, Natalia V.; Федотова, И. Б.; Сурина, Н. М.; Полетаева, И. И.; Kolomytkin, Oleg V.; Mironova, Galina D.

doi:10.1007/s10863-016-9693-5

Cited by 14 publications

(7 citation statements)

References 46 publications

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“…In the pilocarpine-induced model of Status Epilepticus (SE), a reduction of GSH is observed (41, 42), leading to excessive lipid peroxidation in the hippocampus and cortex (43); in kainic acid-induced seizures, there is an overproduction of ROS associated with mitochondrial dysfunction and calcium overload mediated by excessive glutamate receptor activation, leading to the damage of cell structures and alterations including hippocampal lipids and proteins (44). In audiogenically susceptible strains such as GEPRs (acute seizures), a breakdown in hippocampal glutathione peroxidase (GPx) activity has been described, with a decrease in GSH/GSSG ratio (40, 45), while in the whole brain of the Krushinsky-Molodkina (KMs) rat an increased ROS generation by mitochondrial complex I dysfunction was observed (46).…”

Section: Discussionmentioning

confidence: 99%

Energy Metabolism and Redox State in Brains of Wistar Audiogenic Rats, a Genetic Model of Epilepsy

et al. 2019

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The Wistar Audiogenic Rat (WAR) strain is a genetic model of epilepsy, specifically brainstem-dependent tonic-clonic seizures, triggered by acute auditory stimulation. Chronic audiogenic seizures (audiogenic kindling) mimic temporal lobe epilepsy, with significant participation of the hippocampus, amygdala, and cortex. The objective of the present study was to characterize the mitochondrial energy metabolism in hippocampus and cortex of WAR and verify its relationship with seizure severity. Hippocampus of WAR naïve (no seizures) presented higher oxygen consumption in respiratory states related to the maximum capacities of phosphorylation and electron transfer system, elevated mitochondrial density, lower GSH/GSSG and catalase activity, and higher protein carbonyl and lactate contents, compared with their Wistar counterparts. Audiogenic kindling had no adding functional effect in WAR, but in Wistar, it induced the same alterations observed in the audiogenic strain. In the cortex, WAR naïve presented elevated mitochondrial density, lower GSH/GSSG and catalase activity, and higher protein carbonyl levels. Chronic acoustic stimulation in Wistar induced the same alterations in cortex and hippocampus. Mainly in the hippocampus, WAR naïve presented elevated mRNA expression of glucose, lactate and excitatory amino acids transporters, several glycolytic enzymes, lactate dehydrogenase, and Na+/K+ ATPase in neurons and in astrocytes. In vivo treatment with mitochondrial uncoupler 2,4-dinitrophenol (DNP) or N-acetylcysteine (NAC) in WAR had no effect on mitochondrial metabolism, but lowered oxidative stress. Unlike DNP, NAC downregulated all enzyme genes involved in glucose and lactate uptake, and metabolism in neurons and astrocytes. Additionally, it was able to reduce brainstem seizure severity in WAR. In conclusion, in WAR naïve animals, both cerebral cortex and hippocampus display elevated mitochondrial density and/or activity associated with oxidative damage, glucose and lactate metabolism pathways upregulation, and increased Na+/K+ ATPase mRNA expression. Only in vivo treatment with NAC was able to reduce seizure severity of kindled WARs, possibly via down regulation of glucose/lactate metabolism. Taken together, our results are a clear contribution to the field of mitochondrial metabolism associated to epileptic seizures.

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Section: Discussionmentioning

confidence: 99%

Energy Metabolism and Redox State in Brains of Wistar Audiogenic Rats, a Genetic Model of Epilepsy

et al. 2019

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“…Characteristically, this decrease was partially compensated in the "0" rats (Supplementary Figure 2). It was previously shown that KM rats demonstrated reduced ATP production and increased H 2 O 2 levels in the brain and liver compared with W rats (Venediktova et al, 2017). In our study, KM rat mitochondrial disorders also induced an increase in the expression of a number of genes that positively regulate apoptosis (Figure 4).…”

Section: Discussionsupporting

confidence: 72%

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“…This could also signify that some early mutation event occurred rather frequently in rodent brain which affect brain development as a whole, but which is compatible with normal development and function in the absence of sound. This cautious assumption is confirmed by the finding of differences in mitochondrial function in KM rats vs Wistar as well (23). Finally, the KM strain showed the significant decrease in the expression of the Msh3 gene (fig.…”

Section: Resultsmentioning

confidence: 58%

Characteristic Features of the Transcriptome in a Rat Strain with Audiogenic Epilepsy

Chuvakova

Funikov

Давлетшин

et al. 2022

KLS

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Audiogenic epilepsy (AE), developing in rodent strains in response to sound, is widely used as the model of generalized convulsive epilepsy, while the molecular mechanisms determining AE are currently poorly understood. The brain region that is crucial for AE development isthe inferior and superior colliculi (IC, SC). We compared IC-SC gene expression profiles in rats with different AE susceptibility using transcriptome analysis.The transcriptomes were obtained from the IC-SC of Wistar rats (with no AE), Krushinsky-Molodkina (KM) strain rats (100% AE susceptible), and ”0” strain rats (with no AE) selected from F2 KM x Wistar hybrids for AE absence. KM gene expression displayed characteristic differences inboth of the strains that were not susceptible to AE. There was increased expression of a number of genes responsible for positive regulation of the MAPK signaling cascade, as well as of genes responsible for the production of interferon and several other cytokines. An increase in the expression levels of theTTR gene was found in KM rats, as well as significantly lower expression of the Msh3 gene (involved in post-replicative DNA repair systems). AE was also describedin the 101/HY mouse strain with a mutation in the locus controlling DNA repair. The DNA repair system defects could be the primary factor leading to the accumulation of mutations, which, in turn, promote AE. Keywords: udiogenic seizure, KM strain, transcriptome, TTR gene, Msh3 gene, DNA repair

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Energetic, oxidative and ionic exchange in rat brain and liver mitochondria at experimental audiogenic epilepsy (Krushinsky–Molodkina model)

Cited by 14 publications

References 46 publications

Energy Metabolism and Redox State in Brains of Wistar Audiogenic Rats, a Genetic Model of Epilepsy

Energy Metabolism and Redox State in Brains of Wistar Audiogenic Rats, a Genetic Model of Epilepsy

Image_2.TIF

Characteristic Features of the Transcriptome in a Rat Strain with Audiogenic Epilepsy

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