Spike-wave seizures, slow-wave sleep EEG and morphology of substantia nigra pars compacta in WAG/Rij rats with genetic predisposition to absence epilepsy

Evgenia Sitnikova; Elizaveta M Rutskova; Daria Tsvetaeva; Vladimir V Raevsky

doi:10.1016/j.brainresbull.2021.06.003

Spike-wave seizures, slow-wave sleep EEG and morphology of substantia nigra pars compacta in WAG/Rij rats with genetic predisposition to absence epilepsy

Brain Res Bull. 2021 Sep:174:63-71. doi: 10.1016/j.brainresbull.2021.06.003. Epub 2021 Jun 4.

Authors

Evgenia Sitnikova¹, Elizaveta M Rutskova², Daria Tsvetaeva², Vladimir V Raevsky²

Affiliations

¹ Institute of Higher Nervous Activity and Neurophysiology of Russian Academy of Sciences, Butlerova str., 5A, Moscow, 117485, Russia. Electronic address: eu.sitnikova@gmail.com.
² Institute of Higher Nervous Activity and Neurophysiology of Russian Academy of Sciences, Butlerova str., 5A, Moscow, 117485, Russia.

PMID: 34090934
DOI: 10.1016/j.brainresbull.2021.06.003

Abstract

Spike-wave discharges (SWDs) are EEG hallmarks of absence epilepsy, and they spontaneously appear in adult WAG/Rij rats. SWDs are known to be vigilance-dependent and are modulated by monoaminergic mechanisms. It is also known that loss of neurons in the center of the nigrostriatal dopamine system, substantia nigra pars compacta (SNc), is associated with a variety of sleep disorders. We hypothesized that a disorder of the nigrostriatal dopamine system described for WAG/Rij rats might facilitate generation of SWDs through changes in vigilance state and the quality of sleep. Our study was conducted in 'epileptic' and 'non-epileptic' phenotype (less than 1 SWDs per h). Analysis included (1) EEG examination, i.e., analysis of SWDs, rudimentary SWDs and slow wave sleep EEG and (2) microstructural examination of SNc, i.e., measuring its size and the number of neurons and glial cells. No differences in size and cellular content of SNc were found between 'epileptic' and 'non-epileptic' phenotypes. Meanwhile in 'epileptic' subjects, the number of SWDs correlated with the number of neurons in SNc (SWDs more frequently occurred in subjects with fewer neurons in SNc). Rudimentary SWDs were found in both phenotypes. No differences in number and duration of rudimentary SWDs were found between 'epileptic' and 'non-epileptic' phenotypes. Spike-wave EEG activity showed strong association with the number of neurons in SNc: subjects with fewer neurons in SNc were characterized by higher number of SWDs and longer rudimentary SWDs. In sum, our data suggested that intense epileptic EEG activity (in the form of SWDs and rudimentary SWDs) might lead to sleep disruption. However, the lack of direct correlations between sleep parameters and SWDs number indicated that the link between sleep features, SNc cellularity and spike-wave EEG activity could be more complex than we had expected.

Keywords: Absence epilepsy; Animal model; Nigrostriatal dopaminergic system; Slow-wave sleep; Spike-wave discharges; Substantia nigra pars compacta.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Electroencephalography*
Epilepsy, Absence / genetics
Epilepsy, Absence / pathology
Genetic Predisposition to Disease / genetics*
Male
Neurons / pathology
Rats
Rats, Wistar
Seizures / genetics*
Seizures / pathology*
Sleep, Slow-Wave / genetics*
Substantia Nigra / pathology*