Maternal Methyl-Enriched Diet Increases Dopaminergic Tone of the Mesolimbic Brain System in Adult Offspring of WAG/Rij Rats.

The aim of this study is to find out whether maternal methyl-enriched diet affects the content of monoamines and their metabolites in brain structures of adult WAG/Rij offspring. It has been shown for the first time that maternal methyl-enriched diet (choline, betaine, folic acid, vitamin B12, L-methionine, zink) during the perinatal period increases dopaminergic tone of the mesolimbic brain system in adult offspring of WAG/Rij rats, which is accompanied by the suppression of the symptoms of genetic absence epilepsy and comorbid depression. Results suggest that maternal methyl-enriched diet during the perinatal period may be served as a new therapeutic strategy to prevent the development of a hypofunction of the mesolimbic dopaminergic brain system and associated genetic absence epilepsy and comorbid depression in offspring.

Gender-Dependent Effect of Maternal Methyl-Enriched Diet on the Expression of Genetic Absence Epilepsy and Comorbid Depression in Adult Offspring of WAG/Rij Rats.

In the present study it has been shown for the first time that maternal methyl-enriched diet (choline, betaine, folic acid, vitamin B12, L-methionine, zinc) during perinatal period reduces the expression of genetic absence epilepsy and comorbid depression in adult offspring of WAG/Rij rats. This beneficial effect was more pronounced in males compared with females. It is assumed that epigenetic modifications induced by maternal methyl-enriched diet in the offspring at the early stages of ontogenesis might be a possible mechanism underlying the correction of genetically-based pathologic phenotype in WAG/Rij rats. Results suggest that methyl-enriched diet during perinatal period can be potentially used for mitigation or prevention epileptogenesis and depression-like comorbid disorders in people genetically predisposed to absence epilepsy.

Rearing by foster Wistar mother with high level of maternal care counteracts the development of genetic absence epilepsy and comorbid depression in WAG/Rij rats.

It has been shown for the first time that rearing by a foster Wistar mother with high level of maternal care (MC) counteracts the expression of genetic absence epilepsy (AE) and comorbid depression - reduces the number, duration and index of spike-wave discharges (SWDs) and immobility time in the forced swimming test, as well as exerts substantial effects on morphology and time-frequency dynamics of SWDs in WAG/Rij rats. It is supposed that increases in MC early in development might be used to counteract epileptogenesis and comorbid depression in people genetically predisposed to AE.

Lateral asymmetry of early seizure manifestations in experimental generalized epilepsy.

Reorganization of seizure networks during epileptogenesis involves cortico-subcortical and interhemispheric interactions. In the audiogenic kindling (AK) model of generalized tonic-clonic seizures, upstream seizure propagation along ascending brainstem-to-forebrain pathways determines progressive intensification of repeated sound-induced convulsions. Full-blown audiogenic seizures are bilaterally symmetric and their repetition results in bisynchronous recruiting the cortex in secondary epileptogenesis. The present study describes lateral asymmetry of initial behavioral and EEG manifestations of audiogenic seizures and AK in Wistar and WAG/Rij rats with acoustic hypersensitivity. These rats exhibit consistent individual lateralization of running seizures (run directionality) induced by repeated binaural stimulation. Since this initial preconvulsive running reflects seizure onset in the auditory brainstem, the running asymmetry suggests non-symmetric early epileptic activation of brainstem substrates by sound in these rats. Repetition of the asymmetric brainstem seizures led to asynchronous recruiting the cortex into seizure network and lateralization of running seizures was predictive for asymmetry of early cortical seizure manifestations in Wistar and WAG/Rij rats. Both electrographic markers of AK, spreading depression (SD) and post-running afterdischarge, first appeared in the cortex ipsilateral to run direction, suggesting lateralized brainstem-to-forebrain seizure generalization during AK. At the population level, no bias in lateralization of running and SD was found in Wistar and WAG/Rij rats but incidence of secondary cortical seizures varied, depending on strain and run laterality. Among Wistar rats, cortical seizures developed more rarely in right-runners than in left-runners, suggesting enhanced resistance of the right hemisphere to epileptogenesis in rats of this strain. WAG/Rij rats with mixed (absence and audiogenic) epilepsy showed weak lateralization of early cortical seizures and no left-right difference in their incidence during AK. Present findings suggest (1) lateralized brainstem-to-forebrain seizure propagation and hemispheric difference in its facility in Wistar rats, (2) alterations of intra- and interhemispheric seizure propagation in WAG/Rij rats with genetic absence epilepsy.

[Are WAG/Rij rats with genetic absence epilepsy anxious?].

Behavior of susceptible and non-susceptible to audiogenic (convulsive) seizures rats from inbred WAG/Rij strain, genetically predisposed to absence epilepsy, and outbred Wistar strain, genetically not predisposed to absence epilepsy, was compared to assess the level of anxiety (in open field, light-dark choice and elevated plus-maze tests) and the level of depressiveness (in the sucrose consumption and forced swimming tests). Increased level of anxiety was found only in susceptible to audiogenic seizures rats both from WAG/Rij and Wistar strain, but increased level of depressiveness was found only in WAG/Rij strain rats as compared with Wistar rats independently of their susceptibility to audiogenic seizures. Results suggest that increased depressiveness in WAG/Rij strain rats is associated with absence epilepsy but increased anxiety with susceptibility to audiogenic seizures.

Convulsive and nonconvulsive epilepsy in rats: effects on behavioral response to novelty stress.

Behavioral response to a new environment of Wistar and WAG/Rij rats with absence and/or audiogenic seizures (AGSs) was investigated. Behavior was observed in open-field (OF) and light-dark choice (LD) tests. Correlations of test performance with seizure parameters were evaluated. AGS-susceptible Wistar rats exhibited reduced exploration (rearing) in both tests and a tendency toward hyperlocomotion in the OF test. Genetically absence-epileptic WAG/Rij rats demonstrated agitation (increased vertical/horizontal locomotion, enhanced defecation/urination) in the LD test, whereas they exhibited reduced exploration, increased grooming, and hyperlocomotion in the OF test. Anxiety level, as estimated by grooming time in the OF test and latency to first "risk assessment" in the LD test, correlated positively with the propensity for absence seizures in WAG/Rij rats not susceptible to AGSs. It can be concluded that the behavioral response to novelty stress in epileptic subjects depends on the type and severity of seizures.