Person: GÜLÇEBİ İDRİZ OĞLU, MEDİNE
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GÜLÇEBİ İDRİZ OĞLU
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Publication Metadata only 6-Hidroksidopamin Uygulanan Wistar Ve Genetik Absans Epilepsili SıçanlarınRotasyonlarının Karşılaştırılması(2020-11-06) GÜLHAN, REZZAN; GÜLÇEBİ İDRİZ OĞLU, MEDİNE; TOPLU A., YAVUZ M., ÇULPAN Y., TURGAN AŞIK Z. N., GÜLHAN R., GÜLÇEBİ İDRİZ OĞLU M., ONAT F.GİRİŞ VE AMAÇ: 6-Hidroksidopamin (6-OHDA); nigro-striatal dopaminerjik nöronlar için toksik bir ajandır ve Parkinson hastalığının modellenmesinde kullanılır (1). Çalışmamızda, Strasbourg orijinli genetik absans epilepsili sıçanlarda (GAERS) ve Wistar sıçanlarda 6-OHDA toksisitesinin dopaminerjik hasar oluşturmasının göstergelerinden biri olan ve subkutan apomorfinle indüklenen rotasyon davranışını, 2 grup arasında kıyaslamak hedeflendi. YÖNTEM:Bu çalışmada, 30 günlük Wistar ve GAERS hayvanlar kendi içlerinde iki gruba ayrıldı. 6-OHDA (8 µg doz ve 4 µL/4dk hızında); GAERS-MFB (n=8) grubuna medial ön beyin demetine (MFB) (AP:-1,4; ML:1,6; V:7,1 mm) tek enjeksiyon, GAERS-Striatum (n=5) grubuna striatuma iki enjeksiyon (AP:-0,5/+0,5; ML:3,0; V:5,0 mm), Wistar-MFB (n=4) grubuna (AP:-1,4; ML:1,6; V:7,1 mm) tek enjeksiyon, Wistar-Striatum (n=2) grubuna da striatuma iki enjeksiyon (AP:-0,5/+0,5; ML:3,0; V:5,0 mm) olacak şekilde stereotaksik cerrahi yöntemle uygulandı.6-OHDA uygulamasından 21 gün sonra tüm hayvanlara apomorfin enjeksiyonu (0,05 mg/kg, subkutan) uygulandı. Apomorfin uygulanmasından sonra 30 dakika boyunca hayvanların 3600 sağa ve sola rotasyonları kaydedildi. Veriler ortalama±standart hata olarak ifade edildi. Tek yönlü ANOVA ve Tukey’in post-hoc testi kullanıldı (p<0,05 anlamlı olarak kabul edildi). BULGULAR:GAERS-MFB rotasyon sayısı dakikada ortalama 6,56±0,05 iken, GAERS-Striatum dakikada ortalama 6,19±1,72 oldu. Wistar-MFB rotasyon sayısı dakikada ortalama 4,74±2,33 iken, Wistar-Striatum rotasyon sayısı dakikada ortalama 3,27±1,40 olarak bulundu. Gruplar arasında istatistiksel olarak anlamlı bir fark bulunmadı. TARTIŞMA VE SONUÇ:Bulgular; gruplar arasında bir fark olmadığını göstermekle beraber, çalışmamızda grup sayılarının sınırlı olması nedeniyle, sayı arttırılarak çalışmanın devamı hedeflenmektedir. Çalışma TÜBİTAK (218S653) tarafından desteklenmektedir.Publication Open Access Electron microscopic GABA evaluation in hippocampal mossy terminals of genetic absence epilepsy rats receiving kindling stimulations(2022-12-01) KAYA, ÖZLEM TUĞÇE; TURGAN AŞIK, ZEHRA NUR; KARAMAHMUTOĞLU, TUĞBA; GÜLÇEBİ İDRİZ OĞLU, MEDİNE; AKAKIN, DİLEK; ŞİRVANCI, SERAP; İmdat N. N., KAYA Ö. T., TURGAN AŞIK Z. N., ERYİĞİT KARAMAHMUTOĞLU T., GÜLÇEBİ İDRİZ OĞLU M., AKAKIN D., ONAT F., ŞİRVANCI S.Objective: The hypotheses related to the fact of epileptic mechanisms are mainly based on excitation-inhibition imbalance in central nervous system. GAERS (Genetic Absence Epilepsy Rats from Strasbourg) is a well-known animal model of absence epilepsy, and frequently used in experimental studies. In the present study, we aimed to examine possible morphological and gamma-aminobutyric acid (GABA) density changes in GAERS hippocampus after electrical kindling stimulations. Methods: All control and test group rats received 6 kindling stimulations. Rats were decapitated 1 h after the last stimulation. Ultrastructural GABA immunocytochemistry was used to evaluate GABA density quantitatively in mossy terminals of hippocampal CA3 region. Results: GABA levels were less in kindling groups compared to their controls, and in GAERS groups compared to Wistar groups; mitochondrial and dendritic spine area ratios were greater in GAERS groups compared to Wistar groups, although all these evaluations were statistically nonsignificant. Depletion of synaptic vesicles was evident in the mossy terminals of kindling groups. Conclusion: The reason of decreased levels of GABA found in the present study might be that GABA has been released from the synaptic pool rapidly at an early time period after the last stimulation, for compansation mechanisms. Depletion of synaptic vesicles observed in kindling groups shows that even 6 kindling stimulations have an impact of changing hippocampal morphology in trisynaptic cycle. The increased mitochondrial area in GAERS might be related to the increased mitochondrial activity. The increased dendritic spine area might be related to the increased performance of learning in GAERS. Our findings indicating that absence epilepsy and temporal lobe epilepsy have different mechanisms of epileptogenesis might be a basis for further experimental studies.Publication Open Access The role of the substantia nigra pars reticulata in kindling resistance in rats with genetic absence epilepsy(WILEY, 2015-11) ONAT, FİLİZ; Akman, Ozlem; Gulcebi, Medine I.; Carcak, Nihan; Ozatman, Sema Ketenci; Eryigit, Tugba; Moshe, Solomon L.; Galanopoulou, Aristea S.; Onat, Filiz YilmazObjectiveGenetic 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.Publication Metadata only Genetik absans epilepsili ve epileptik olmayan sıçanlarda nigrostriatal yolak dejenerasyonunun kalretinin immunoreaktivitesi üzerine etkisi(2022-11-10) KİRAZLI, ÖZLEM; GÜLÇEBİ İDRİZ OĞLU, MEDİNE; ŞEHİRLİ, ÜMİT SÜLEYMAN; GÜLHAN, REZZAN; KİRAZLI Ö., Turgan Aşık Z. N., Çulpan Y., GÜLÇEBİ İDRİZ OĞLU M., ŞEHİRLİ Ü. S., GÜLHAN R., ONAT F.Amaç: Kalsiyum bağlayıcı proteinler, nöronal işlev ve nörogenezde önemli rol oynamaktadır. Kalretinin, dikensiz GABAerjik internöronlarda eksprese edilmekte ve gelen dopaminerjik afferentlerle ve glutamaterjik kortikostriatal afferentlerle sinaptik bağlantı kurmaktadır. Yaşla birlikte azalabilen kalretinin, ileri yaşlardaki motor fonksiyonda oluşacak kayıplardan sorumlu tutulabilmektedir. Parkinson modeli sıçanlarda nigro -striatal yolaktaki dopaminerjik nöron kaybı sonrasında striatumda bulunan kalretinin pozitif internöronlarda azalma meydana geldiği gösterilmiştir. Bu azalışa glutamat reseptörlerindeki aşırı aktivite ve dopaminin eksikliğinin neden olduğu iddia edilmiştir. Kalretinin pozitif internöronların temporal epilepsiye karşı hassas olduğu gösterilmiştir. Epileptogenez sürecinde kimyasal lezyon ile nigro-striatal yolağın devre dışı bırakılmasının kalretinin sentezleyen nöronlar üzerine etkisi incelenmiştir. Gereç ve Yöntem: Striatum, Substantia Nigra pars compacta ve pars reticulata da bulunan kalretinin içeren nöronların tespiti için medial ön beyin demetine 6-OHDA uygulanan Wistar (n=5) GAERS (n=5) Wistar kontrol (n=5) ve GAERS kontrol (n=5) 40µm’lik sıçan beyin kesitlerine immohistokimya yöntemi uygulanmıştır. Nöronların sayım işlemleri floresans boyanmış kesitler üzerinden yapılmıştır. İstatistiksel değerlendirme için GraphPad Prism Tek yönlü ANOVA ve gruplar arasındaki karşılaştırma kullanılmıştır. Bulgular: Çalışmamızda (6 –OHDA) enjekte edilen Wistar ve GAERS sıçanlarda kontrol gruplarına göre kalretinin pozitif hücre sayısında azalma gözlenmiştir. Bu azalma Striatum için istatistiksel olarak anlamlı bulunmazken, Substantia Nigra pars compacta (p<0,05) ve pars reticulata (p<0,05) için anlamlıdır. Sonuç: Literatürde (6 –OHDA) enjekte edilen sıçanlarda nigrostriatal yolakta sağlam kalan dopaminerjik nöronların kalretinin eksprese ettiği gözlemlenmiştir. Bu sonuçlar sonrasında, kalretininin nöroprotektif etkisinden dolayı dopaminerjik nöronları koruyabildiği ileri sürülebilir.Publication Metadata only Changes in intracellular protein expression in cortex., thalamus and hippocampus in a genetic rat model of absence epilepsy(PERGAMON-ELSEVIER SCIENCE LTD, 2011) OGAN, AYŞE; Danis, Ozkan; Demir, Serap; Gunel, Aslihan; Aker, Rezzan Gulhan; Gulcebi, Medine; Onat, Filiz; Ogan, AyseEpilepsy is a chronic disorder characterized by repeated seizures resulting from abnormal activation of neurons in the brain. Although mutations in genes related to Na+, K+, Ca2+ channels have been defined, few studies show intracellular protein changes. We have used proteomics to investigate the expression of soluble proteins in a genetic rat model of absence epilepsy Genetic Absence Epilepsy Rats from Strasbourg (GAERS). The advantage of this technique is its high throughput quantitative and qualitative detection of all proteins with their post-translational modifications at a given time. The parietal cortex and thalamus, which are the regions responsible for the generation of absence seizures, and the hippocampus, which is not involved in this activity, were dissected from GAERS and from non-epileptic control rat brains. Proteins from each tissue sample were isolated and separated by two-dimensional gel electrophoresis. Spots that showed significantly different levels of expression between controls and GAERS were identified by nano LC-ESI-MS/MS. Identified proteins were: ATP synthase subunit delta and the 14-3-3 zeta isoform in parietal cortex; myelin basic protein and macrophage migration inhibitory factor in thalamus; and macrophage migration inhibitory factor and 0-beta 2 globulin in hippocampus. All protein expressions were up-regulated in GAERS except 0-beta globulin. These soluble proteins are related to energy generation, signal transduction, inflammatory processes and membrane conductance. These results indicate that not only membrane proteins but also cytoplasmic proteins may take place in the pathophysiology and can be therapeutic targets in absence epilepsy. (C) 2011 Elsevier Inc. All rights reserved.Publication Metadata only Absans epilepsinin epileptogenez sürecinde nigro-striatal dopaminerjik yolağın rolünün araştırılması(2021-05-27) YANANLI, HASAN RACİ; GÜLHAN, REZZAN; GÜLÇEBİ İDRİZ OĞLU, MEDİNE; TOPLU A., YAVUZ M., ÇULPAN Y., TURGAN AŞIK Z. N., YANANLI H. R., GÜLHAN R., GÜLÇEBİ İDRİZ OĞLU M., ONAT F.Epilepsinin ve epileptogenezin patogenezinde rol alan nöronal mekanizmaların ortaya konması güncel hedeflerden bir tanesidir. Bu çalışmada non-konvülsif nöbetlerle karakterize absans epilepsisinin epileptogenez döneminde nigro-striatal dopaminerjik yolağın rolünün ortaya konması hedeflenmiştir. Bu amaçla Strasbourg kökenli genetik absans epilepsili sıçanların (GAERS) ve kontrol grubunu oluşturan Wistar sıçanların mediyal önbeyin demetine (MFB) 6-Hidroksidopamin (6-OHDA) verilmesi ile ortaya çıkan sonuçlar kıyaslanmıştır. Yöntemler: Deneylerde 30 günlük GAERS(n=5) ve Wistar sıçanlar(n=2) kullanıldı. Stereotaksik cerrahiyle 6-OHDA (8 µg/4µL/4dk hızında) MFB’ye (AP:-1,4; ML:1,6; V:7,1) enjekte edildi. Gruplarda 21 gün sonra adımlama, silindir ve rotasyon testleri yapıldı. Silindir testi için pleksiglas silindire alınan hayvanların sağ ve sol ön pençeleriyle silindire değme sayısı gözlendi. Adımlama testi için 50 cm parkurda tek ön pençesiyle ilerlemesi sağlanarak (diğer pençeler tutularak) adım sayısı hesaplandı. Rotasyon testi öncesi tüm hayvanlara apomorfin (0,05 mg/kg, subkutan) enjeksiyonu yapılarak 30 dakika boyunca hayvanların 3600 sola dönüşleri kaydedildi. Veriler ortalama±standart hata olarak belirtildi. Spearman korelasyon testi ile istatistiksel değerlendirme yapıldı. Bulgular: GAERS grubu için rotasyon sayısı 257,8±39,98; adımlama testinde adım sayısı sol 10±4,25, sağ 11,8±3,21 idi. Silindire değme testinde ön pençe değme sayısı sol 8,2±2,39, sağ 9,4±2,37 idi. Wistar grubu için rotasyon sayısı 245±89; adımlama testinde adım sayısı sol 0, sağ 5±4 idi. Silindire değme testinde ön pençe değme sayısı sol 7,5±1,5, sağ 11±3 idi. Gruplar arasında anlamlı bir korelasyon bulunmadı. Sonuçlar: 6-OHDA enjekte edilen sıçanların rotasyon testi ile adımlama ve silindir testleri arasında anlamlı bir korelasyon bulunamadı. Çalışmamızda grup sayılarının sınırlılığı nedeniyle, sayı arttırılarak çalışmanın devamı hedeflenmektedir. Çalışma TÜBİTAK (218S653) tarafından desteklenmektedir. Anahtar Kelimeler: GAERS, absans epilepsisi, rotasyon, adımlama, silindir testi Objective: One of the aims in the neuroscience is to define the neuronal mechanisms involved in the pathogenesis of epilepsy and epileptogenesis. In this study, we examined the role of the nigrostriatal dopaminergic pathway in the epileptogenesis of absence epilepsy characterized by non-convulsive seizures. We compared the findings of injection of 6-Hydroxydopamine (6-OHDA) to the medial forebrain bundle (MFB) of the Strasbourg genetic absence epilepsy rats (GAERS) with the control Wistar rats. Methods: The MFB (AP:-1.4; ML:1.6; V:7.1) of 30-days-old GAERS(n=5) and Wistar(n=2) animals were targeted and injected with 6-OHDA(8 µg/4µL/4min) by stereotaxic surgery. After 21 days, cylinder, stepping and rotation tests were performed. For the cylinder test, the number of right and left front paw touch to the plexiglass cylinder were counted separately from the animals which were observed for 20 min. For the stepping test, the number of steps taken was calculated by driving the animals on a single front paw (right and left front paws were calculated separately). Afterwards, all animals received an injection of apomorphine (0.05 mg/kg), and the rotation(3600) of animals were recorded for 30 min. Data were expressed as mean±standart error. Spearman correlation was performed. Results: In GAERS group, number of rotations were 257.8±40.0. In the stepping test, the left steps were 10±4.25; while the right were 11.8±3.21.In the cylinder test, the number of front paw touches with left paw were 8.2±2.39; and the right were 9.4±2.37. For the Wistar group, number of rotations were 245±89. In the stepping test, the left steps were 0; the right were 5±4. And the number of front paw touches left were 7.5±1.5; the right were 11±3 with no significant correlation between the groups. Conclusions: No significant correlation was found between rotation behavior and the stepping-cylinder test of animals. In the study, group numbers are planned to be increased. The study is supported by TUBITAK (218S653).Publication Metadata only Ultrastructural GABA immunocytochemistry in the mossy fiber terminals of Wistar and genetic absence epileptic rats receiving amygdaloid kindling stimulations(ELSEVIER, 2011) AKAKIN, DİLEK; Akakin, Dilek; Sirvanci, Serap; Gurbanova, Ayten; Aker, Rezzan; Onat, Filiz; San, TangulThe existence of absence epilepsy and temporal lobe epilepsy in the same patient is not common in clinical practice. The reason why both types of seizures are rarely seen in the same patient is not well understood. Therefore, we aimed to investigate kindling in a well known model of human absence epilepsy, genetic absence epilepsy rats from Strasbourg (GAERS). In the present study, we analyzed whether the GABA content of GAERS that received kindling stimulations was altered in the hippocampal mossy fiber terminals compared to non-epileptic control (NEC) Wistar rats. For this purpose, we used an immunocytochemical technique at the ultrastructural level. Ultrathin sections were immunolabeled with anti-GABA antibody and transmission electron microscopy was used for the ultrastructural examination. The number of gold particles per nerve terminal was counted and the area of the nerve terminal was determined using NIH image analysis program. The GABA density was found to be higher in sham-operated GAERS than sham-operated Wistar rats. The density was increased in kindling Wistar group compared to sham-operated Wistar and kindling GAERS groups. No statistical difference was observed between sham-operated GAERS and kindling GAERS groups. The increase in GABA levels in stimulated Wistar rats may be a result of a protective mechanism. Furthermore, there may be strain differences between Wistar rats and GAERS and our findings addressing different epileptogenesis mechanisms in these strains might be a basis for future experimental studies. (C) 2010 Elsevier B.V. All rights reserved.Publication Open Access The effect of prenatal and postnatal caffeine exposure on pentylentetrazole induced seizures in the non-epileptic and epileptic offsprings(2019-11-01) GÜLÇEBİ İDRİZ OĞLU, MEDİNE; ONAT, FİLİZ; YAVUZ M., Albayrak N., Ozgur M., Oglu M., Cavdar S., Onat F.Caffeine, a central nervous system stimulant, has been reported to modulate seizure activity in various studies. In this study the effects of caffeine exposure on the pentylenetetrazole (PTZ) induced seizure thresholds and seizure stages in the Wistar and genetic absence epilepsy model offsprings were examined. Adult female and male Wistar rats and genetic absence epilepsy rats from Strasbourg (GAERS) consumed caffeine dissolved in water (0.3 g/L) before conception, during the gestational periods and lactation period whereas control groups of each strain received tap water. All offsprings at postnatal day 30 (PN30) subjected to 70 mg/kg of PTZ were evaluated in terms of overall seizure stages, the latency to the first generalized seizure and the c-Fos protein activity in the brain regions of somatosensorial cortex (SSCx), reticular thalamic nucleus (Rt), ventrobasal thalamus (VB), centromedial nucleus (CM) and lateral geniculate nucleus (LGN). The Wistar caffeine group had significantly shorter latency to the first generalized seizure (1.53 +/- 0.49 min) comparing to the Wistar control offsprings (3.40 +/- 0.68 min). GAERS caffeine group (6.52 +/- 2.48 min) showed significantly longer latency comparing to Wistar caffeine group (1.53 +/- 0.49 min). Although statistically not significant, GAERS caffeine group showed a longer latency comparing to the GAERS control group (4.71 +/- 1.82 min). In all regions of SSCx, Rt, VB, CM and LGN, GAERS caffeine group had lower c-Fos protein expression comparing to the GAERS control group (p < 0.05). Wistar caffeine rats had lower expression of c-Fos protein comparing to the Wistar control group only in SSCx. In CM, GAERS rats expressed lower c-Fos protein comparing to the Wistar control (p < 0.05). In conclusion differential effects of caffeine in the seizure modulation may involve c-Fos protein activity-dependent protection mechanisms.Publication Open Access Evaluation of GAD67 immunoreactivity in the region of substantia nigra pars reticulata in resistance to development of convulsive seizure in genetic absence epilepsy rats(KARE PUBL, 2016) ONAT, FİLİZ; Gulcebi, Medine; Akman, Ozlem; Carcak, Nihan; Karamahmutoglu, Tugba; Onat, FilizOBJECTIVE: Nonconvulsive absence epilepsy and convulsive epilepsy seizures are rarely seen in the same patient. It has been demonstrated that there is a resistance to development of convulsive seizures in genetic absence epilepsy models. The present study investigated glutamic acid decarboxylase (GAD) immunoreactivity in the brain region related to the interaction of these two seizure types, namely substantia nigra pars reticulata (SNR) subregions, SNRantenor and SNRpostenor. METHODS: Nonepileptic adult male Wistar rats and Genetic Absence Epilepsy Rats from Strasbourg (GAERS) were used. Experimental groups of Wistar and GAERS were electrically stimulated for kindling model to induce convulsive epileptic seizures. An electrical stimulation cannula was stereotaxically implanted to the basolateral amygdala and recording electrodes were placed on the cortex. Sagittal sections of SNR were used to evaluate immunohistochemical reaction. Sections were incubated with anti-GAD67 antibody. Densitometric analysis of GAD67 immunoreactive neurons was performed using photographs of stained sections. One-way analysis of variance and post hoc Bonferroni test were used for statistical analysis of the data. RESULTS: There was no difference in GAD67 immunoreactivity of SNR subregions of control Wistar and control GAERS. An increase in GAD67 immunoreactivity was detected in SNRposterior subregion of stimulated Wistar rats, whereas there was a decrease in GAD67 immunoreactivity in SNRposterior of stimulated GAERS. The difference in GAD67 immunoreactivity between these two groups was statistically significant. CONCLUSION: Level of synthetized gamma-aminobutyric acid in SNRposterior subregion plays an important role in the interaction of nonconvulsive absence epilepsy seizures and convulsive epilepsy seizures.