The role of ovarian steroid hormones in the regulation of basal and stress induced absence seizures

Tolmacheva, E.A.; Luijtelaar, Gilles van

doi:10.1016/j.jsbmb.2007.03.017

Cited by 18 publications

(10 citation statements)

References 30 publications

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“…First of all, seizures are absent during any motor activity including ambulation/exploration but abundantly present during behavioral inactivity/immobility associated with quiet wakefulness and drowsiness (Drikenburg et al., 1991; Van Luijtelaar et al., 1991). Moreover, acute stress and corticosteroids actively suppress absence seizures for at least 15 min (Schridde & van Luijtelaar, 2004b; Tolmacheva & van Luijtelaar, 2007). Secondly, absence seizures do not cause statistically significant decreases in ambulatory activity: in the number of squares crossed (open field test), in the number of transitions between compartments (light–dark choice test), or in the number of approaches to the drinking bottle (sucrose consumption test).…”

Section: Discussionmentioning

confidence: 99%

Spike–wave discharges are necessary for the expression of behavioral depression‐like symptoms

et al. 2009

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SUMMARYPurpose: The WAG/Rij strain of rats, a wellestablished model for absence epilepsy, has comorbidity for depression. These rats exhibit depression-like behavioral symptoms such as increased immobility in the forced swimming test and decreased sucrose intake and preference (anhedonia). These depression-like behavioral symptoms are evident in WAG/Rij rats, both at 3-4 and 5-6 months of age, with a tendency to aggravate in parallel with an increase in seizure duration. Here we investigated whether the behavioral symptoms of depression could be prevented by the suppression of absence seizures. Methods: Ethosuximide (ETX; 300 mg/kg/day, in the drinking water) was chronically applied to WAG/Rij rats from postnatal day 21 until 5 months. Behavioral tests were done before the cessation of the treatment. Electroencephalography (EEG) recordings were made before and after cessation of treatment to measure seizure severity at serial time-points. Results: ETX-treated WAG/Rij rats exhibited no symptoms of depression-like behavior in contrast to untreated WAG/Rij rats of the same age. Moreover, treated WAG/Rij rats did not differ from control age-matched Wistar rats. ETX treatment led to almost complete suppression of spike-wave discharges (SWDs) in 5-6 month old WAG/Rij rats. Discontinuation of chronic treatment was accompanied by a gradual emergence of SWDs; however, a persistent reduction in seizure activity was still present 47 days after discontinuation of the chronic treatment. Discussion: The results suggest that seizure activity is necessary for the expression of depression-like behavioral symptoms and confirm that epileptogenesis can be prevented by early and chronic treatment.

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Section: Discussionmentioning

confidence: 99%

Spike–wave discharges are necessary for the expression of behavioral depression‐like symptoms

et al. 2009

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“…The implication of the results is that acute stress decreases the responses of area CA3 neurons to afferent input, and in so doing, blocks the ability to detect differences that are due to gonadal hormones such as estradiol. An impairment by stress of the acute effects of progesterone administration has been described in Wag/Rij rats (Tolmacheva and van Luijtelaar, 2007). If one were to generalize from these observations to humans, one would predict that an individual who is behaviorally stressed may not show the same cycle-dependent effects as an individual who is not stressed.…”

Section: Why Are Experimental Conditions So Important To Researchmentioning

confidence: 99%

Sex differences in the neurobiology of epilepsy: A preclinical perspective

Scharfman

MacLusky

2014

Neurobiology of Disease

130

111

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When all of the epilepsies are considered, sex differences are not always clear, despite the fact that many sex differences are known in the normal brain. Sex differences in epilepsy in laboratory animals are also unclear, although robust effects of sex on seizures have been reported, and numerous effects of gonadal steroids have been shown throughout the rodent brain. Here we discuss several reasons why sex differences in seizure susceptibility are unclear or are difficult to study. Examples of robust sex differences in laboratory rats, such as the relative resistance of adult female rats to the chemoconvulsant pilocarpine compared to males, are described. We also describe a novel method that has shed light on sex differences in neuropathology, which is a relatively new techniques that will potentially contribute to sex differences research in the future. The assay we highlight uses the neuronal nuclear antigen NeuN to probe sex differences in adult male and female rats and mice. In females, weak NeuN expression defines a sex difference that previous neuropathological studies have not described. We also show that in adult rats, social isolation stress can obscure the normal effects of 17β-estradiol to increase excitability in area CA3 of hippocampus. These data underscore the importance of controlling behavioral stress in studies of seizure susceptibility in rodents and suggest that behavioral stress may be one factor that has led to inconsistencies in outcomes of sex differences research. These and other issues have made it difficult to translate our increasing knowledge about the effects of gonadal hormones on the brain to improved treatment for men and women with epilepsy.

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“…demonstrated in mice that compared with estrus, the high progesterone diestrus state was associated with higher hippocampal δ subunit expression and lower γ2 subunit expression as well as associated increased tonic current amplitudes (Maguire et al, 2005). Although the hippocampus is not thought to play a direct role in the expression of typical absence seizures, it is involved in atypical absence seizures and it modulates typical absence seizures (Stewart et al, 2009; Wu et al, 2007; Tolmacheva and van Luijtelaar, 2007a,b). In addition, it is possible that the increased δ subunit expression seen in the hippocampus during diestrus would also be seen in the relay nuclei of the thalamus and thereby cause an enhanced tonic current which would exacerbate absence seizures.…”

Section: The Role Of Stressors Sex Steroids and Phosphorylation In Gmentioning

confidence: 99%

“…Castrated males showed more SWD activity than intact males and ovariectomized and intact females, suggesting that testosterone protects males against absence seizures (van Luijtelaar et al, 1996). Others compared intact and ovariectomized female WAG/Rij rats and showed either an increase in SWD one week after the removal of the ovaries (Kayim Yildiz et al, 2013), or no change in SWD frequency 4 to 35 days post-surgery but an aggravation of SWD in ovariectomized rats after repeated exposure to stressors (Tolmacheva and van Luijtelaar, 2007a). The reason for the lack of consistent outcomes in females (either no effects, or an increase) is not immediately clear.…”

Section: Role Of Sex Hormones On Absence Epilepsy and Seizuresmentioning

confidence: 99%

Animal models of absence epilepsies: What do they model and do sex and sex hormones matter?

Luijtelaar

Onat

Gallagher

2014

Neurobiology of Disease

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While epidemiological data suggest a female prevalence in human childhood- and adolescence-onset typical absence epilepsy syndromes, the sex difference is less clear in adult-onset syndromes. In addition, although there are more females than males diagnosed with typical absence epilepsy syndromes, there is a paucity of studies on sex differences in seizure frequency and semiology in patients diagnosed with any absence epilepsy syndrome. Moreover, it is unknown if there are sex differences in the prevalence or expression of atypical absence epilepsy syndromes. Surprisingly, most studies of animal models of absence epilepsy either did not investigate sex differences, or failed to find sex-dependent effects. However, various rodent models for atypical syndromes such as the AY9944 model (prepubertal females show a higher incidence than prepubertal males), BN model also with a higher prevalence in males and the Gabra1 deletion mouse in the C57BL/6J strain offer unique possibilities for the investigation of the mechanisms involved in sex differences. Although the mechanistic bases for the sex differences in humans or these three models are not yet known, studies of the effects of sex hormones on seizures have offered some possibilities. The sex hormones progesterone, estradiol and testosterone exert diametrically opposite effects in genetic absence epilepsy and pharmacologically-evoked convulsive types of epilepsy models. In addition, acute pharmacological effects of progesterone on absence seizures during proestrus are opposite to those seen during pregnancy. 17β-Estradiol has anti-absence seizure effects, but it is only active in atypical absence models. It is speculated that the pro-absence action of progesterone, and perhaps also the delayed pro-absence action of testosterone, are mediated through the neurosteroid allopregnanolone and its structural and functional homolog, androstanediol. These two steroids increase extrasynaptic thalamic tonic GABAergic inhibition by selectively targeting neurosteroid-selective subunits of GABAA receptors (GABAARs). Neurosteroids also modulate the expression of GABAAR containing the γ2, α4, and δ subunits. It is hypothesized that differences in subunit expression during pregnancy and ovarian cycle contribute to the opposite effects of progesterone in these two hormonal states.

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The role of ovarian steroid hormones in the regulation of basal and stress induced absence seizures

Cited by 18 publications

References 30 publications

Spike–wave discharges are necessary for the expression of behavioral depression‐like symptoms

Spike–wave discharges are necessary for the expression of behavioral depression‐like symptoms

Sex differences in the neurobiology of epilepsy: A preclinical perspective

Animal models of absence epilepsies: What do they model and do sex and sex hormones matter?

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