Impaired postnatal development of the hippocampus of Krushinsky-Molodkina rats genetically prone to audiogenic seizures

Kulikov, Alexey A.; Дорофеева, Н. А.; Naumova, A. A.; Harbachova, Eugenia L.; Глазова, М. В.; Chernigovskaya, E. V.

doi:10.1016/j.yebeh.2020.107526

Cited by 10 publications

(9 citation statements)

References 49 publications

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“…An increased apoptosis rate in the inferior colliculi in KM rats compared to W was previously described ( Chernigovskaya et al, 2018 ). This increase in apoptosis rate may be associated with abnormal brain development in KM rats, which in turn may be the cause of epileptogenesis, this effect was experimentally demonstrated in inferior colliculi and hippocampus of KM rats ( Chernigovskaya et al, 2018 ; Kulikov et al, 2020 ). The delay in IC development was also demonstrated, in line with apoptosis, ( Kulikov et al, 2020 ).…”

Section: Discussionmentioning

confidence: 90%

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: Discussionmentioning

confidence: 90%

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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“…According to the literature data, the end of the second postnatal week is a period when normal morphogenesis of both the IC and hippocampus is generally completed, although some developmental processes continue up to the end of the first month [21,23,37,38]. Our previous data revealed that two-week-old KM rats still demonstrated increased proliferation and apoptosis in the IC and hippocampus indicating the delayed maturation of these structures in comparison to normal (Wistar) rats [27,28]. Moreover, our previous studies showed that in the IC of KM rats at this time point the expression of GAD67 was similar to the control indicating no alterations in GABA synthesis, but the number of PV-positive cells was reduced pointing on decreased activity of GABAergic cells [29].…”

Section: Th Postnatal Day (P15)mentioning

confidence: 99%

“…In particular, when exerting a depolarizing effect, GABA can stimulate migration of both glutamatergic and GABAergic neurons, while growth of KCC2 expression and decrease of intracellular Cl¯ stops migration of cells [52]. Our previous results revealed impaired migration of newborn glutamatergic cells in the hippocampus of 15-day-old KM rats which led to abnormally high number of these cells in the hilus both in young and adult animals [28]. Thus, our present data let to suppose that these changes could be associated with prolonged excitatory action of GABA in a large number of the hippocampal cells during first two postnatal weeks.…”

Section: Th Postnatal Day (P15)mentioning

confidence: 99%

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Dysregulation of GABAergic System in the Hippocampus and Inferior Colliculi of Rats during the Development of Audiogenic Epilepsy

Ivlev

Chernigovskaya

Nikolaeva

et al. 2023

Preprint

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Epilepsy is tightly associated with dysfunction of inhibitory γ-aminobutyric acid (GABA) neurotransmission. In this study, Krushinsky-Molodkina (KM) rats genetically prone to audiogenic seizures (AGS) were used. KM rats are characterized by the development of audiogenic epilepsy during postnatal ontogenesis, with AGS onset at the age of 1.5-2 months and fully developed AGS expression by 3rd month. We analyzed GABAergic system of the inferior colliculi (IC) and the hippocampus of KM rats at different stages of postnatal development. Wistar rats were used as a control. In the IC of young KM rats, Na+/K+/Cl- cotransporter 1 (NKCC1) expression was increased, while in adults K+/Cl- cotransporter 2 (KCC2) was downregulated indicating impairment of postsynaptic GABA action both at early and later stages of postnatal development. In the hippocampus of young KM rats, we observed a decrease in activity of GABAergic neurons and downregulation of KCC2 and NKCC1. Adult rats, in opposite, demonstrated elevated activity of the hippocampal GABAergic cells and unchanged expression of chlorine transporters indicating upregulation of GABA transmission. Thus, GABA dysregulation in the IC can mediate the seizure susceptibility in adult KM rats, while in the hippocampus, upregulation of GABAergic system can restrict the spreading of epileptiform activity from the brainstem.

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“…This increase in apoptosis rate may be associated with abnormal brain development in KM rats, which in turn may be the cause of epileptogenesis, this effect was experimentally demonstrated in inferior colliculi and hippocampus of KM rats (Chernigovskaya et al, 2018;Kulikov et al, 2020). The delay in IC development was also demonstrated, in line with apoptosis, (Kulikov et al, 2020).…”

Section: Discussionmentioning

confidence: 82%

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Impaired postnatal development of the hippocampus of Krushinsky-Molodkina rats genetically prone to audiogenic seizures

Cited by 10 publications

References 49 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

Dysregulation of GABAergic System in the Hippocampus and Inferior Colliculi of Rats during the Development of Audiogenic Epilepsy

Table_2.xlsx

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