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

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dc.contributor.authorONAT, FİLİZ
dc.contributor.authorsvan Luijtelaar, Gilles; Onat, Filiz Yilmaz; Gallagher, Martin J.
dc.date.accessioned2022-03-10T11:39:32Z
dc.date.available2022-03-10T11:39:32Z
dc.date.issued2014-12
dc.description.abstractWhile 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 Gabral 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. 17 beta-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 GABA(A) receptors (GABA(A)Rs). Neurosteroids also modulate the expression of GABA(A)R containing the gamma 2, alpha 4, and delta 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. (C) 2014 Elsevier Inc All rights reserved.
dc.identifier.doi10.1016/j.nbd.2014.08.014
dc.identifier.eissn1095-953X
dc.identifier.issn0969-9961
dc.identifier.pubmed25132554
dc.identifier.urihttps://hdl.handle.net/11424/219877
dc.identifier.wosWOS:000345198200007
dc.language.isoeng
dc.publisherACADEMIC PRESS INC ELSEVIER SCIENCE
dc.relation.ispartofNEUROBIOLOGY OF DISEASE
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectGenetic models
dc.subjectAbsence epilepsy
dc.subjectRats
dc.subjectWAG/Rij
dc.subjectMice
dc.subjectAtypical absence models
dc.subjectTypical absence models
dc.subjectAY 9944
dc.subjectSex differences
dc.subjectPuberty
dc.subjectNeurosteroids
dc.subjectPregnancy
dc.subjectOvarian cycle
dc.subjectGABA(A) receptors
dc.subjectDelta subunits
dc.subjectAlpha subunits
dc.subjectSPIKE-WAVE DISCHARGES
dc.subjectGABA(A) RECEPTOR GAMMA-2-SUBUNIT
dc.subjectSEIZURE SUSCEPTIBILITY
dc.subjectSTEROID-HORMONES
dc.subjectAFTERDISCHARGE THRESHOLDS
dc.subjectGENERALIZED EPILEPSIES
dc.subjectSUBUNIT EXPRESSION
dc.subjectMATERNAL-BEHAVIOR
dc.subjectRETICULAR NUCLEUS
dc.subjectANGELMAN SYNDROME
dc.titleAnimal models of absence epilepsies: What do they model and do sex and sex hormones matter?
dc.typereview
dspace.entity.typePublication
local.avesis.ida16db493-099d-46b4-b15e-b7989e878efd
local.import.packageSS4
local.indexed.atWOS
local.indexed.atSCOPUS
local.indexed.atPUBMED
local.journal.numberofpages13
oaire.citation.endPage179
oaire.citation.startPage167
oaire.citation.titleNEUROBIOLOGY OF DISEASE
oaire.citation.volume72
relation.isAuthorOfPublicationc359dea3-046f-4397-90d5-62e4bfc31869
relation.isAuthorOfPublication.latestForDiscoveryc359dea3-046f-4397-90d5-62e4bfc31869

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