The lower expression of parvalbumin in the primary somatosensory cortex of WAG/Rij rats may facilitate the occurrence of absence seizures

Arkan, Sertan; Kasap, Murat; Akman, Özlem; Akpınar, Gürler; Ateş, Nurbay; Karson, Ayşe

doi:10.1016/j.neulet.2019.134299

Cited by 7 publications

(5 citation statements)

References 22 publications

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“…Such mutations are more likely to produce deficits in neuronal maturation and migration, thereby possibly resulting in improper neural circuit formation and epilepsy. Indeed, cilia dysfunction resulting from the selective loss of ciliary GTPase Arl13b affects cilia growth and also reduces the morphological complexity of parvalbumin-positive interneurons [31], a subset of inhibitory neurons implicated in multiple forms of epilepsy [32][33][34]. Similarly, we hypothesize that CILK1 variants that promote ciliary growth by dominant-negative mechanisms will promote similar interneuronal deficits that promote JME.…”

Section: Discussionmentioning

confidence: 88%

Mice Harboring a Non-Functional CILK1/ICK Allele Fail to Model the Epileptic Phenotype in Patients Carrying Variant CILK1/ICK

Salvati

Mason

Gailey

et al. 2021

IJMS

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CILK1 (ciliogenesis associated kinase 1)/ICK (intestinal cell kinase) is a highly conserved protein kinase that regulates primary cilia structure and function. CILK1 mutations cause a wide spectrum of human diseases collectively called ciliopathies. While several CILK1 heterozygous variants have been recently linked to juvenile myoclonic epilepsy (JME), it remains unclear whether these mutations cause seizures. Herein, we investigated whether mice harboring either a heterozygous null Cilk1 (Cilk1+/−) mutation or a heterozygous loss-of-function Cilk1 mutation (Cilk1R272Q/+) have epilepsy. We first evaluated the spontaneous seizure phenotype of Cilk1+/− and Cilk1R272Q/+ mice relative to wildtype littermates. We observed no electrographic differences among the three mouse genotypes during prolonged recordings. We also evaluated electrographic and behavioral responses of mice recovering from isoflurane anesthesia, an approach recently used to measure seizure-like activity. Again, we observed no electrographic or behavioral differences in control versus Cilk1+/− and Cilk1R272Q/+ mice upon isoflurane recovery. These results indicate that mice bearing a non-functional copy of Cilk1 fail to produce electrographic patterns resembling those of JME patients with a variant CILK1 copy. Our findings argue against CILK1 haploinsufficiency being the mechanism that links CILK1 variants to JME.

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Section: Discussionmentioning

confidence: 88%

Mice Harboring a Non-Functional CILK1/ICK Allele Fail to Model the Epileptic Phenotype in Patients Carrying Variant CILK1/ICK

Salvati

Mason

Gailey

et al. 2021

IJMS

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“…PV + interneurons are an important cellular element influencing neuronal network excitability in different brain regions ( Bartholome et al. 2020 ) and the occurrence of absence seizures in rats ( Arkan et al. 2019 ).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, GAERS and WAG/Rij rats revealed marked alterations in the density of parvalbumin-positive (PV + ) interneurons in different cortical and hippocampal regions ( Papp et al. 2018 ; Arkan et al. 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Modulation of pacemaker channel function in a model of thalamocortical hyperexcitability by demyelination and cytokines

et al. 2022

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A consensus is yet to be reached regarding the exact prevalence of epileptic seizures or epilepsy in multiple sclerosis (MS). In addition, the underlying pathophysiological basis of the reciprocal interaction among neuroinflammation, demyelination, and epilepsy remains unclear. Therefore, a better understanding of cellular and network mechanisms linking these pathologies is needed. Cuprizone-induced general demyelination in rodents is a valuable model for studying MS pathologies. Here, we studied the relationship among epileptic activity, loss of myelin, and pro-inflammatory cytokines by inducing acute, generalized demyelination in a genetic mouse model of human absence epilepsy, C3H/HeJ mice. Both cellular and network mechanisms were studied using in vivo and in vitro electrophysiological techniques. We found that acute, generalized demyelination in C3H/HeJ mice resulted in a lower number of spike–wave discharges, increased cortical theta oscillations, and reduction of slow rhythmic intrathalamic burst activity. In addition, generalized demyelination resulted in a significant reduction in the amplitude of the hyperpolarization-activated inward current (Ih) in thalamic relay cells, which was accompanied by lower surface expression of hyperpolarization-activated, cyclic nucleotide-gated channels, and the phosphorylated form of TRIP8b (pS237-TRIP8b). We suggest that demyelination-related changes in thalamic Ih may be one of the factors defining the prevalence of seizures in MS.

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“…Concerning the studied neuronal populations, it is not known to what extent their recorded quantitative variability depended on actual numerical changes or on the expression levels of their markers, which are also of functional importance (Arkan et al., 2019 ; Barinka et al., 2010 : Gall et al., 2003 ; Schwaller et al., 2004 ). The detected decreases in the density of N‐PV+ and N‐CR+ could have been the final result of decreases in neuronal production and/or seizure‐induced degeneration, or of decreases in the expression of the marker proteins which are also of functional importance (Dobolyi et al., 2014 ; Marksteiner et al., 1989 ).…”

Section: Discussionmentioning

confidence: 99%

Structural changes in the neocortex as correlates of variations in EEG spectra and seizure susceptibility in rat brains with different degrees of dysplasia

Setkowicz

Gzieło

Kielbinski

et al. 2021

J of Comparative Neurology

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Disturbances of the early stages of neurogenesis lead to irreversible changes in the structure of the mature brain and its functional impairment, including increased excitability, which may be the basis for drug‐resistant epilepsy. The range of possible clinical symptoms is as wide as the different stages of disturbed neurogenesis may be. In this study, we used a quadruple model of brain dysplasia by comparing structural and functional disorders in animals whose neurogenesis was disturbed with a single dose of 1 Gy of gamma rays at one of the four stages of neurogenesis, that is, on days 13, 15, 17, or 19 of prenatal development. When reached adulthood, the prenatally irradiated rats received EEG teletransmitter implantation. Thereafter, pilocarpine was administered and significant differences in susceptibility to seizure behavioral symptoms were detected depending on the degree of brain dysplasia. Before, during, and after the seizures significant correlations were found between the density of parvalbumin‐immunopositive neurons located in the cerebral cortex and the intensity of behavioral seizure symptoms or increases in the power of particular EEG bands. Neurons expressing calretinin or NPY showed also dysplasia‐related increases without, however, correlations with parameters of seizure intensity. The results point to significant roles of parvalbumin‐expressing interneurons, and also to expression of NPY—an endogenous anticonvulsant and neuroprotectant reducing susceptibility to seizures and supporting neuronal survival.

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The lower expression of parvalbumin in the primary somatosensory cortex of WAG/Rij rats may facilitate the occurrence of absence seizures

Cited by 7 publications

References 22 publications

Mice Harboring a Non-Functional CILK1/ICK Allele Fail to Model the Epileptic Phenotype in Patients Carrying Variant CILK1/ICK

Mice Harboring a Non-Functional CILK1/ICK Allele Fail to Model the Epileptic Phenotype in Patients Carrying Variant CILK1/ICK

Modulation of pacemaker channel function in a model of thalamocortical hyperexcitability by demyelination and cytokines

Structural changes in the neocortex as correlates of variations in EEG spectra and seizure susceptibility in rat brains with different degrees of dysplasia

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