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GÜLHAN, REZZAN

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Now showing 1 - 10 of 11
  • PublicationOpen Access
    The pathways connecting the hippocampal formation, the thalamic reuniens nucleus and the thalamic reticular nucleus in the rat
    (WILEY, 2008-03) ONAT, FİLİZ; Cavdar, Safiye; Onat, Filiz Y.; Cakmak, Yusuf Oezguer; Yananli, Hasan R.; Gulcebi, Medine; Aker, Rezzan
    Most dorsal thalamic nuclei send axons to specific areas of the neocortex and to specific sectors of the thalamic reticular nucleus; the neocortex then sends reciprocal connections back to the same thalamic nucleus, directly as well indirectly through a relay in the thalamic reticular nucleus. This can be regarded as a 'canonical' circuit of the sensory thalamus. For the pathways that link the thalamus and the hippocampal formation, only a few comparable connections have been described. The reuniens nucleus of the thalamus sends some of its major cortical efferents to the hippocampal formation. The present study shows that cells of the hippocampal formation as well as cells in the reuniens nucleus are retrogradely labelled following injections of horseradish peroxidase or fluoro-gold into the rostral part of the thalamic reticular nucleus in the rat. Within the hippocampal formation, labelled neurons were localized in the subiculum, predominantly on the ipsilateral side, with fewer neurons labelled contralaterally. Labelled neurons were seen in the hippocampal formation and nucleus reuniens only after injections made in the rostral thalamic reticular nucleus (1.6-1.8 mm caudal to bregma). In addition, the present study confirmed the presence of afferent connections to the rostral thalamic reticular nucleus from cortical (cingulate, orbital and infralimbic, retrosplenial and frontal), midline thalamic (paraventricular, anteromedial, centromedial and mediodorsal thalamic nuclei) and brainstem structures (substantia nigra pars reticularis, ventral tegmental area, periaqueductal grey, superior vestibular and pontine reticular nuclei). These results demonstrate a potential for the thalamo-hippocampal circuitry to influence the functional roles of the thalamic reticular nucleus, and show that thalamo-hippocampal connections resemble the circuitry that links the sensory thalamus and neocortex.
  • PublicationOpen Access
    Amygdala kindling in the WAG/Rij rat model of absence epilepsy
    (WILEY, 2006-01) ONAT, FİLİZ; Aker, RG; Yananli, HR; Gurbanova, AA; Ozkaynakci, AE; Ates, N; van Luijtelaar, G; Onat, FY
    Purpose: The kindling model in rats with genetic absence epilepsy is suitable for studying mechanisms involved in the propagation and generalization of seizure activity in the convulsive and nonconvulsive components of epilepsy. In the present study, we compared the amygdala kindling rate and afterdischarge characteristics of the nonepileptic Wistar control rat with a well-validated model of absence epilepsy, the WAG/Rij rat, and demonstrated the effect of amygdala kindling on spike-and-wave discharges (SWDs) in the WAG/Rij group. Methods: Electrodes were stereotaxically implanted into the basolateral amygdala of rats for stimulation and recording and into the cortex for recording. After a recovery period, the animals were stimulated at their afterdischarge thresholds. EEG was recorded to analyze SWDs and afterdischarge durations. The seizure severity was evaluated by using Racine's 5-stage scale. Results: All nonepileptic control and four of seven WAG/Rij animals reached a stage 5 seizure state, whereas three animals failed to reach stage 3, 4, or 5 and stayed at stage 2 after application of 30 stimulations. Interestingly, WAG/Rij rats, resistant to kindling, demonstrated a significantly longer duration of SWDs on the first day of the experiment before kindling stimulation than did the kindled WAG/Rij animals. Additionally, the cumulative total duration and the number of SWDs after the kindling stimulation were statistically increased compared with SWDs before kindling stimulation. Conclusions: The results of our study demonstrate that the progress of amygdala kindling is changed in rats with genetic absence epilepsy, perhaps as a consequence of the hundreds of daily SWDs.
  • Publication
    Effect of U-92032, T-Type Ca(2+)Channel Blocker, on Rats with Genetic Absence Epilepsy
    (KARGER, 2020) YANANLI, HASAN RACİ; Yananli, Hasan Raci; Demirkapu, Mahluga Jafarova; Sakalli, Halil Eren; Gulhan, Rezzan; Onat, Filiz Yilmaz
    Introduction:Absence epilepsy is associated with diffuse spike-and-wave discharges (SWD) on the electroencephalogram (EEG). Recent studies have demonstrated that the primary somatosensory cortex is also implicated in the generation of the SWDs.Objective:This study investigated the effects of systemic and local administrations of U-92032 into the brain of Genetic Absence Epilepsy Rats from Strasbourg (GAERS).Methods:GAERS animals underwent stereotaxic surgery for the placement of EEG recording electrodes and guide cannulas for U-92032 administration into the lateral ventricle (intracerebroventricular [i.c.v.]), upper lips area (S1Ulp) or barrel field area (S1B) of primary somatosensory cortex. Following 7 days of recovery, electrical activity was recorded continuously for 1 h before and 6 h after intraperitoneal (0.25; 1; 5 mg/kg i.p.) or local U-92032 or dimethyl sulfoxide (DMSO) injections.Results:No changes were detected in the cumulative duration, mean duration, and number of SWDs following i.p. U-92032 injections. Local i.c.v. injections of U-92032 caused a significant decrease in the cumulative duration (i.c.v., 50 and 100 nmol/L), mean duration (i.c.v., 50, 100, and 250 nmol/L), and the number (i.c.v., 250 nmol/L) of SWDs compared to DMSO groups. Intra-cortical (S1Ulp and S1B) U-92032 injections caused a significant decrease in all 3 parameters compared to DMSO groups, as well.Conclusion:Intra-cortical injection of U-92032 caused almost complete removal of SWDs in GAERS and i.c.v. administration resulted in a significant reduction. However, systemic i.p. administration did not cause a significant change with the applied -doses.
  • PublicationOpen Access
    Connections of the zona incerta to the reticular nucleus of the thalamus in the rat
    (WILEY, 2006-08) ONAT, FİLİZ; Cavdar, Safiye; Onat, Filiz; Cakmak, Yusuf Ozgur; Saka, Erdinc; Yananli, Hasan R.; Aker, Rezzan
    This study demonstrated that there is a pathway from the zona incerta to the thalamic reticular nucleus. Injections of horseradish peroxidase or Fluorogold were made, using stereotaxic coordinates, into the rostral, intermediate or caudal regions of the thalamic reticular nucleus of adult Sprague-Dawley rats. The results show that the different regions of the thalamic reticular nucleus have distinct patterns of connections with the sectors of the zona incerta. In terms of the relative strength of the connections, injections made into the rostral regions of the thalamic reticular nucleus showed the highest number of labelled cells within the rostral and ventral sectors of the zona incerta; injections made into the intermediate regions of the thalamic reticular nucleus showed labelled cells in the dorsal and ventral sectors; while injections to the caudal regions of the thalamic reticular nucleus showed only a few labelled cells in the caudal sector of the zona incerta. Previous studies have shown that the zona incerta projects to the higher order thalamic nuclei but not first order thalamic nuclei. The labelling observed in the present study may represent collaterals of zona incerta to higher order thalamic nuclei projections.
  • PublicationOpen Access
    THE EFFECTS OF TOPIRAMATE APPLIED TO THE NUCLEUS ACCUMBENS_x000D_ REGION ON MORPHINE WITHDRAWAL SYNDROME
    (2020-08-28) YANANLI, HASAN RACİ; Songül ÖZKULA;Hasan Raci YANANLI;Rezzan GÜLHAN;Oya Helin DUNDAR;Selçuk EROL;Ramazan BAKAR;Heja GECİT;N. Eymen TURAN;M. Fırat BALIK;Mahluga JAFAROVA DEMİRKAPU
    Aim: Nucleus accumbens, one of the nuclei of the basal ganglia, and dopamine, the neurotransmitter play a critical role in opioiddependence and withdrawal. In opioid withdrawal, the importance of neurotransmitters such as glutamate and gamma aminobutyric acid(GABA), as well as dopamine, is known. In this study, we aimed to investigate the effects of local injections of topiramate, anantiepileptic agent affecting GABAergic and glutamatergic pathways, into the nucleus accumbens on withdrawal signs and locomotoractivity during naloxone-induced withdrawal in morphine-dependent rats.Materials and Methods: Twenty male Sprague-Dawley rats were divided in topiramate treatment and control groups. All animalsreceived morphine pellets and guide cannulas were placed bilaterally in the nucleus accumbens regions by stereotaxic surgery. On thelast day of the experiment, following the bilateral topiramate or saline (control group) microinjections, morphine withdrawal was triggeredby naloxone.Results: Topiramate microinjections into the nucleus accumbens region significantly suppressed the signs of naloxone-inducedmorphine withdrawal such as number of jumpings and weight loss. No significant difference was observed in wet dog shakes, one of thewithdrawal signs, after local topiramate treatment. Although topiramate microinjections increased stereotypical activity it did not changelocomotor activity behavior such as vertical and ambulatory activity, and total covered distance.Conclusion: These findings show that local microinjection of topiramate into the nucleus accumbens is effective in preventing opioiddeprivation symptoms without significant effect on locomotor activity.
  • Publication
    Extracellular concentrations of catecholamines and amino acids in the dorsomedial hypothalamus of kindled rats - A Microdialysis Study
    (KARGER, 2003) ONAT, FİLİZ; Goren, MZ; Aker, R; Yananli, HR; Onat, FY
    Epilepsy affects homeostasis and autonomic nervous system functions. It has been thought that the dysfunction in the autonomic neural mechanisms could be a cause of sudden unexpected death in patients with epilepsy. The kindling model of epilepsy is considered to be an animal model for complex partial seizures with secondary generalization. The objectives of this study were to investigate the extracellular gamma-aminobutyric acid (GABA), glutamate, noradrenaline and dopamine levels in the dorsomedial nucleus of the hypothalamus in nonepileptic and kindled epileptic rats and to explain some of the cardiovascular changes in the kindling model of epilepsy. Stimulation electrodes were stereotaxically implanted into the basolateral amygdala and electrical stimulation was applied 3 times a day at a constant current. The rats were then kindled to full stage 5 seizures. Microdialysis experiments were performed to demonstrate the neurotransmitter levels in the dorsomedial nucleus of the hypothalamus 3-5 days after being kindled. Decreases in noradrenaline and dopamine levels in the dorsomedial nucleus were detected in the conscious kindled animals. This finding is in agreement with prior findings that the noradrenergic system has a negative role in the process of kindling. The basal level of glutamic acid and GABA remained unchanged in the kindled group when compared to non-epileptic animals, and similarly, neither blood pressure nor heart rate responses to bicuculline or N-methyl-D-aspartate were affected by the acute kindled state. These findings suggest that the autonomic changes in kindling require further studies. Copyright (C) 2003 S. Karger AG, Basel.
  • Publication
    GABA(A) receptor mediated transmission in the thalamic reticular nucleus of rats with genetic absence epilepsy shows regional differences: Functional implications
    (ELSEVIER SCIENCE BV, 2006) ONAT, FİLİZ; Aker, Rezzan Gulhan; Ozyurt, Hazan B.; Yananli, Hasan R.; Cakmak, Yusuf Ozgur; Ozkaynakci, Aydan E.; Sehirli, Umit; Saka, Erdinc; Cavdar, Safiye; Onat, Filiz Yimaz
    The aim of the present study was to investigate the effect of local injections of the GABA(A) receptor antagonist, bicuculline, into the rostral and caudal parts of the thalamic reticular nucleus (TRN), on the generation of spike-and-wave discharges in Genetic Absence Epilepsy Rats from Strasbourg (GAERS). Spike-and-wave discharges are important in the pathophysiology of absence epilepsy and generated by the cortico-thalamo-cortical pathway, where GABA has a significant role, particularly in the TRN. Artificial cerebrospinal fluid or bicuculline was administered to rostral or caudal parts of TRN of GAERS through a stereotaxically placed guide cannula. Administration of bicuculline produced opposite effects according to the injection site. Administration into the caudal TRN produced statistically significant increases in the duration of spike-and-wave discharges, whereas injections into the rostral TRN produced significant decreases. Correspondingly, distinct patterns of afferent connections have been demonstrated with the wheat-germ-agglutinin horseradish peroxidase (WGA-HRP) retrograde tracing method in control non-epileptic rats and GAERS for the rostral and caudal parts of the TRN. Injection of WGA-HRP tracer showed no detectable difference regarding the rostral and caudal connections between GAERS and Wistar animals. Rostral parts of TRN have thalamic and cortical connections that are primarily motor and limbic whereas for the caudal parts these connections are primarily sensory. Further, the rostral parts receive inputs from the substantia nigra pars reticularis and the ventral pallidum that the caudal part lacks. The extent to which these connectional differences may be responsible for the functional differences demonstrated by the bicucculine injections remains to be explored. (c) 2006 Elsevier B.V. All rights reserved.
  • PublicationOpen Access
    The afferent connections of the posterior hypothalamic nucleus in the rat using horseradish peroxidase
    (WILEY, 2001-04) ONAT, FİLİZ; Cavdar, S; Onat, F; Aker, R; Sehirli, U; San, T; Yananli, HR
    The posterior hypothalamic nucleus has been implicated as an area controlling autonomic activity. The afferent input to the nucleus will provide evidence as to its role in autonomic function. in the present study, we aimed to identify the detailed anatomical projections to the posterior hypothalamic nucleus from cortical, subcortical and brainstem structures, using the horseradish peroxidase (HRP) retrograde axonal transport technique in the rat, Subsequent to the injection of HRP into the posterior hypothalamic nucleus, extensive cell labelling was observed bilaterally in various areas of the cerebral cortex including the cingulate, frontal, parietal and insular cortices. At subcortical levels: labelled cells were observed in the medial and lateral septal nuclei, the bed nucleus of stria terminalis, and various thalamic and amygdaloid nuclei. Also axons of the vertical and horizontal limbs of the diagonal band were labelled and labelled cells were localised at the CA1 and CA3 fields of the hippocampus and the dentate gyrus. The brainstem projections were from the medial, lateral and parasolitary nuclei, the intercalated nucleus of the medulla, the sensory nuclei of the trigeminal nerve, and various reticular, vestibular, raphe and central rey nuclei. The posterior hypothalamic nucleus also received projections from the lateral and medial cerebellar nuclei and from upper cervical spinal levels. The results are discussed in relation to the involvement of the posterior hypothalamic nucleus in autonomic function and allows a better understanding of how the brain controls visceral function.
  • Publication
    The effect of telmisartan, an angiotensin receptor blocker, on alcohol consumption and alcohol-induced dopamine release in the nucleus accumbens
    (ELSEVIER SCIENCE INC, 2020) YANANLI, HASAN RACİ; Tezcan, Kutluhan; Yananli, Hasan Raci; Demirkapu, Mahluga Jafarova; Goren, M. Zafer; Sakalli, H. Eren; Colombo, Giancarlo; Gulhan, Rezzan
    Alcohol use disorder remains a major health problem. The mesocorticolimbic dopaminergic system, including the nucleus accumbens region and multiple neural circuits, is involved in its complex underlying mechanism. For instance, alcohol intake stimulates the central and peripheral renin-angiotensin system and increases angiotensin II levels, which predominantly affect angiotensin 1 receptors both in the periphery and in the brain. In this study, we aimed to investigate the effects of the intracerebroventricularly-administered angiotensin 1 receptor blocker telmisartan on the alcohol consumption of male Sardinian alcohol-preferring (sP) rats and on the alcohol-induced dopamine levels in the nucleus accumbens region in Wistar rats. Acute intracerebroventricular administration of telmisartan (100 nM) reduced the alcohol intake for 24 hours without affecting food and water consumption in sP rats. Acute intracerebroventricular injection of the opioid receptor antagonist naloxone (75 nM), tested as a reference compound, also reduced the alcohol consumption in sP rats; however, naloxone's effect lasted only for 30 minutes. In microdialysis experiments, telmisartan administered intracerebroventricularly did not change dopamine levels in the nucleus accumbens that had been induced by acute intraperitoneal alcohol administration in Wistar rats. According to these results, further studies are needed to elucidate the role of the renin-angiotensin system on alcohol use disorder pathophysiology. (c) 2021 Elsevier Inc. All rights reserved.
  • Publication
    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).