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dc.contributor.authorAkman, Ozlem
dc.contributor.authorGulcebi, Medine I.
dc.contributor.authorCarcak, Nihan
dc.contributor.authorOzatman, Sema Ketenci
dc.contributor.authorEryigit, Tugba
dc.contributor.authorMoshe, Solomon L.
dc.contributor.authorOnat, Filiz Yilmaz
dc.date.accessioned2019-08-13T12:10:23Z
dc.date.accessioned2019-08-13T15:58:00Z
dc.date.available2019-08-13T12:10:23Z
dc.date.available2019-08-13T15:58:00Z
dc.date.issued2015
dc.identifier.issn0013-9580
dc.identifier.issn1528-1167
dc.identifier.urihttps://dx.doi.org/10.1111/epi.13204
dc.identifier.urihttp://hdl.handle.net/11446/2619
dc.descriptionWOS: 000363884100025en_US
dc.descriptionPubMed ID: 26471261en_US
dc.description.abstractObjectiveGenetic Absence Epilepsy Rats from Strasbourg (GAERS) show a resistance to secondary generalization of focal limbic seizures evoked by kindling. The substantia nigra pars reticulata (SNR) is involved in the propagation and modulation of seizures in kindling. We first examined the role of the SNRanterior and SNRposterior subregions in the resistance to the development of kindling in GAERS. Subsequently, to determine whether kindling resistance relates to differential sensitivity of -aminobutyric acid -aminobutyric acid (GABA)ergic or dopaminergic SNR neurons to kindling, we studied the effects of kindling-inducing stimulations on parvalbumin (PRV; GABAergic neuron marker) or tyrosine hydroxylase (TH; dopaminergic neuron marker) immunoreactivity (ir), respectively, in GAERS and in nonepileptic control (NEC) Wistar rats that lack kindling resistance. MethodsAdult male GAERS were implanted with a stimulation electrode in the amygdala, and bilateral injection cannulas for lidocaine or saline injection (30 min before each kindling stimulation until the animals reached three stage 5 seizures or the 22 stimulations) into the SNRanterior or SNRposterior. In another experiment, PRV-ir in SNRanterior and SNRposterior and TH-ir in SNRposterior only were densitometrically compared in GAERS-SHAM, NEC-SHAM GAERS-STIM, and NEC-STIM animals (6 kindling stimulations). ResultsBilateral SNRposterior infusions of lidocaine eliminated the kindling resistance and resulted in stage 5 generalized motor seizures in all kindled rats. Bilateral lidocaine infusions in the SNRanterior failed to alter the kindling resistance in GAERS. PRV-ir in the SNRposterior was unaltered in GAERS-STIM but increased in NEC-STIM group. Cellular TH-ir in the SNRposterior significantly increased by kindling stimulations in both NEC-STIM and GAERS-STIM groups. SignificanceThe kindling resistance in GAERS is mediated by the SNRposterior in a lidocaine-sensitive manner. The insensitivity to kindling stimulation of PRV-ir in SNRposterior of GAERS but not NEC rats, implicate GABAergic SNRposterior neurons in kindling resistance. In contrast, the observed stimulation-specific increase in TH-ir in the SNRposterior is unrelated to kindling resistance.en_US
dc.description.sponsorshipScientific and Technological Research Council of Turkey (TUBITAK) [111S209]; Marmara University Research Council; National Institute of Neurological Disorders and Stroke (NINDS) [NS078333, NS020253]; U.S. Department of Defense [W81XWH-13-1-0180]; Citizens United for Research in Epilepsy (CURE), UCB; Heffer Family Foundation; Barry Segal Family Foundation; Abbe Goldstein/Joshua Lurie and Laurie Marsh/Dan Levitz families; NINDS [NS078333, NS091170]; CURE, UCBen_US
dc.description.sponsorshipThis study was supported by The Scientific and Technological Research Council of Turkey (TUBITAK), Project No: 111S209, and Marmara University Research Council. SLM received research grants from the National Institute of Neurological Disorders and Stroke (NINDS; NS078333, NS020253), U.S. Department of Defense (W81XWH-13-1-0180), Citizens United for Research in Epilepsy (CURE), UCB, the Heffer Family and Barry Segal Family Foundations, and the Abbe Goldstein/Joshua Lurie and Laurie Marsh/Dan Levitz families. ASG received research grants from NINDS (NS078333, NS091170), U.S. Department of Defense (W81XWH-13-1-0180), CURE, UCB, the Heffer Family and Barry Segal Family Foundations, and the Abbe Goldstein/Joshua Lurie and Laurie Marsh/Dan Levitz families.en_US
dc.language.isoengen_US
dc.publisherWILEYen_US
dc.identifier.doi10.1111/epi.13204en_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectGAERSen_US
dc.subjectKindling resistanceen_US
dc.subjectSubstantia nigra pars reticulataen_US
dc.subjectTyrosine hydroxylaseen_US
dc.subjectParvalbuminen_US
dc.titleThe role of the substantia nigra pars reticulata in kindling resistance in rats with genetic absence epilepsyen_US
dc.typearticleen_US
dc.relation.journalEPILEPSIAen_US
dc.departmentDBÜen_US
dc.identifier.issue11en_US
dc.identifier.volume56en_US
dc.identifier.startpage1793en_US
dc.identifier.endpage1802en_US
dc.contributor.authorID0000-0003-0680-4782en_US
dc.contributor.authorID0000-0002-6490-9331en_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.department-temp[Akman, Ozlem] Istanbul Bilim Univ, Fac Med, Dept Physiol, Istanbul, Turkey -- [Gulcebi, Medine I. -- Ozatman, Sema Ketenci -- Eryigit, Tugba -- Onat, Filiz Yilmaz] Marmara Univ, Fac Med, Dept Pharmacol & Clin Pharmacol, TR-34854 Istanbul, Turkey -- [Carcak, Nihan] Istanbul Univ, Fac Pharm, Dept Pharmacol, Istanbul, Turkey -- [Ozatman, Sema Ketenci] Istanbul Bilim Univ, Vocat Sch Hlth Serv, Istanbul, Turkey -- [Moshe, Solomon L. -- Galanopoulou, Aristea S.] Montefiore Epilepsy Management Ctr, Albert Einstein Coll Med, Lab Dev Epilepsy, Saul R Korey Dept Neurol, Bronx, NY USA -- [Moshe, Solomon L. -- Galanopoulou, Aristea S.] Albert Einstein Coll Med, Dominick P Purpura Dept Neurosci, Bronx, NY 10467 USA -- [Moshe, Solomon L. -- Galanopoulou, Aristea S.] Montefiore Med Ctr, Bronx, NY 10467 USA -- [Moshe, Solomon L.] Albert Einstein Coll Med, Dept Pediat, New York, NY USA -- [Onat, Filiz Yilmaz] Marmara Univ, Epilepsy Res Ctr, TR-34854 Istanbul, Turkeyen_US


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