Subthreshold Corazol Doses Induced Generalized Seizures in Audigenic Seizure-Prone Rats

Полетаева, И. И.

doi:10.15436/2377-1348.16.954

Cited by 6 publications

(1 citation statement)

References 29 publications

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“…At the initial stages of "0" strain rat selection, several backcrosses to the KM parental rat strain had been performed (Fedotova et al, 2012) in order to obtain animals with a genetic background more similar to that of KM rats as currently existing Wistar rats differ from KM rats, due to the history of long separate breeding. This "hidden" AE proneness was revealed first, as not 100% of the "0" rats were non-AE-prone, and then, as expected, the AE seizures in the "0" rats developed after induction with a subthreshold dose of penthylenetetrazole (Fedotova et al, 2016;Poletaeva et al, 2017). In accordance with this finding, we used only the rats in the "0" rat strain group that did not respond to sound (see "Materials and Methods" section).…”

Section: Resultsmentioning

confidence: 70%

Transcriptome of the Krushinsky-Molodkina Audiogenic Rat Strain and Identification of Possible Audiogenic Epilepsy-Associated Genes

Chuvakova

Funikov

Rezvykh

et al. 2021

Front. Mol. Neurosci.

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Audiogenic epilepsy (AE), inherent to several rodent strains is widely studied as a model of generalized convulsive epilepsy. The molecular mechanisms that determine the manifestation of AE are not well understood. In the present work, we compared transcriptomes from the corpora quadrigemina in the midbrain zone, which are crucial for AE development, to identify genes associated with the AE phenotype. Three rat strains without sound exposure were compared: Krushinsky-Molodkina (KM) strain (100% AE-prone); Wistar outbred rat strain (non-AE prone) and “0” strain (partially AE-prone), selected from F2 KM × Wistar hybrids for their lack of AE. The findings showed that the KM strain gene expression profile exhibited a number of characteristics that differed from those of the Wistar and “0” strain profiles. In particular, the KM rats showed increased expression of a number of genes involved in the positive regulation of the MAPK signaling cascade and genes involved in the positive regulation of apoptotic processes. Another characteristic of the KM strain which differed from that of the Wistar and “0” rats was a multi-fold increase in the expression level of the Ttr gene and a significant decrease in the expression of the Msh3 gene. Decreased expression of a number of oxidative phosphorylation-related genes and a few other genes was also identified in the KM strain. Our data confirm the complex multigenic nature of AE inheritance in rodents. A comparison with data obtained from other independently selected AE-prone rodent strains suggests some common causes for the formation of the audiogenic phenotype.

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Section: Resultsmentioning

confidence: 70%

Transcriptome of the Krushinsky-Molodkina Audiogenic Rat Strain and Identification of Possible Audiogenic Epilepsy-Associated Genes

Chuvakova

Funikov

Rezvykh

et al. 2021

Front. Mol. Neurosci.

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Neuroinflammation in Pathogenesis of Audiogenic Epilepsy: Altered Proinflammatory Cytokine Levels in the Rats of Krushinsky–Molodkina Seizure-Prone Strain

Сурина

Федотова

Nikolaev

et al. 2023

Biochemistry Moscow

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Neuroinflammation in the pathogenesis of the audiogenic epilepsy: altered proinflammatory cytokine levels in Krushinsky-Molodkina seizure-prone rats

Surina,

Fedotova,

Nikolaev

et al. 2023

Biohimiâ

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Neuroinflammation plays an important role in epileptogenesis, however, most studies are performed on pharmacological models of epilepsy, while data on non-invasive, including genetic, models are practically absent. In Krushinsky-Molodkina (KM) strain rats with high genetically caused predisposition to AE (intensive audiogenic seizure fit in response to the action of sound) and in the control strain “0” (not predisposed to AE), the levels of a number of pro-inflammatory cytokines were investigated using multiplex immunofluorescence magnetic assay (MILLIPLEX map Kit). Cytokine levels were determined in the dorsal striatum tissue and in the brain stem. Background levels of IL-1β, IL-6 and TNF-α in the dorsal striatum of KM rats were significantly lower than in rats “0” (32.31, 27.84 and 38.87% of decrease, respectively, p < 0.05, 0.05 and 0.01), whereas in the brain stem in the “background” state of interstrain differences in levels of these metabolites were not detected. 4 h after sound exposure, the TNF-α level in the dorsal striatum of KM rats was significantly (38.34%, p < 0.01) lower than in “0” rats. In KM rats, after the action of sound and the subsequent seizure fit, the levels of IL-1β and IL-6 in the dorsal striatum were significantly higher compared to the background (35.29 and 50.21%, of increase, p < 0.05, 0.01, respectively). The IL-2 level in KM rats in the background state was not detected, whereas after audiogenic seizures its level was 14.01 pg/ml (significantly higher, p < 0.01). In the brain stem of KM rats, the levels of IL-1β and TNF-α after audiogenic seizures were significantly lower than in the background (13.23 and 23.44% of decrease, respectively, p < 0.05). In rats of the “0” strain, the levels of cytokines in the dorsal striatum after the action of sound (which did not cause AE seizures) did not differ from those in the background, while the levels of IL-1β in their brain stem were lower than in the background (40.28%, p < 0.01). Thus, the differences between the background levels of cytokines and those after the action of sound were different in rats that differed in their predisposition to AE, which suggests the involvement of these metabolites in the pathophysiology of epilepsy.

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Subthreshold Corazol Doses Induced Generalized Seizures in Audigenic Seizure-Prone Rats

Cited by 6 publications

References 29 publications

Transcriptome of the Krushinsky-Molodkina Audiogenic Rat Strain and Identification of Possible Audiogenic Epilepsy-Associated Genes

Transcriptome of the Krushinsky-Molodkina Audiogenic Rat Strain and Identification of Possible Audiogenic Epilepsy-Associated Genes

Neuroinflammation in Pathogenesis of Audiogenic Epilepsy: Altered Proinflammatory Cytokine Levels in the Rats of Krushinsky–Molodkina Seizure-Prone Strain

Neuroinflammation in the pathogenesis of the audiogenic epilepsy: altered proinflammatory cytokine levels in Krushinsky-Molodkina seizure-prone rats

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