Person: ONAT, FİLİZ
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ONAT
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FİLİZ
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Publication Open Access Changes in baroreflex responses of kindled rats(WILEY, 2005-03) ONAT, FİLİZ; Kaya, CA; Ozkaynakci, AE; Goren, MZ; Onat, FYPurpose: This Study was planned to investigate the baroreflex responses (BRs) in kindled rats during seizure-free period to put forward new data on cardiac autonomic changes in epilepsy. Methods: Male Wistar rats were randomized into sham-operated (SO) and kindled groups where stimulation and recording electrodes were implanted stereotaxically into the basolateral amygdala and the cortex, respectively. For kindling process, rats were stimulated twice daily at their afterdischarge threshold current and accepted as being kindled after 10 grade 5 seizures. Six to 8 weeks after the establishment of the kindled state, mean arterial pressure (MAP) and heart rate (HR) were evaluated. BR was defined as the ratio of HR response to changes in MAP induced by i.v. nitroprusside (10, 25 mu g/kg) or i.v. pherylephrine (10, 25 mu g/kg). The sympathetic or parasympathetic component of the BR was evaluated in rats pretreated with atropine or atenolol where phenylephrine or nitroprusside was administered at 25 mu g/kg. Results: Basal MAP and HR values were found to be similar in SO and kindled rats. Phenylephrine increased MAP more in the kindled group (p < 0.05), but the HR decreased similarly in both groups. Nitroprusside decreased MAP at similar rates, but the increase in HR was higher in the kindled rats (p < 0.05). BRs to phenylephrine and nitroprusside were abolished after pretreatment with atenolol and atropine, whereas pherylephrine- and nitroprusside-induced changes in MAP remained unchanged in both groups. Conclusions: These results may indicate that amygdaloid kindling affects BRs in long-term seizure-free periods.Publication Open 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, RezzanMost 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.Publication Open Access Cerebellar connections to the rostral reticular nucleus of the thalamus in the rat(WILEY, 2002-12) ONAT, FİLİZ; Cavdar, S; Onat, FYL; Yananli, HR; Sehirli, US; Tulay, C; Saka, E; Gurdal, EWe studied the cerebellar connections to the reticular nucleus thalamus (RNT) by means of retrograde axonal transport of horseradish peroxidase (HRP) in the rat. Specific HRP pressure injections to the rostral RNT(1.6-1.8 mm caudal to bregma) resulted in retrograde labelling of neurones in the cerebellar nuclei. The rostral RNT showed specific topographical organization of its cerebellar connections. Microinjections into the rostral RNT, 1.6 mm caudal to bregma, produced numerous HRP-labelled neurones within the anterior interposed (emboliform nucleus) and scarce HRP-labelled neurones within the lateral (dentate nucleus) cerebellar nuclei, whereas injections into the rostral RNT, 1.8 mm caudal to bregma, produced numerous HRP-labelled neurones within the posterior interposed (globose nucleus) and scarce lightly HRP-labelled neurones within the lateral (dentate nucleus) cerebellar nuclei. Cerebellar connections with the rostral RNT were exclusively ipsilateral to the injection site. No HRP-labelled cells were detected in the medial (fastigial nucleus) cerebellar nucleus. The cerebellar connections reach the RNT via the superior cerebellar peduncle. By contrast, HRP injections into the anterior, posterior interposed and lateral cerebellar nuclei produced no labelled cells within the RNT. This study demonstrates the existence of direct cerebello-RNT but not RNT-cerebellar connections. The presence of the cerebello-RNT connections introduces a new route through which the cerebellum may influence RNT and thus cerebral cortical activity.Publication Metadata only Electroencephalographic differences between WAG/Rij and GAERS rat models of absence epilepsy(ELSEVIER, 2010) ONAT, FİLİZ; Akman, Ozlem; Demiralp, Tamer; Ates, Nurbay; Onat, Filiz YilmazThe inbred Wistar Albino Glaxo Rats from Rijswijk (WAG/Rij) and the Genetic Absence Epilepsy Rats from Strasbourg (GAERS) are well-validated genetic models of absence epilepsy. Although they share similar characteristics including the spike-and-wave discharges (SWDs) in the EEG, some differences have been reported between both strains. This study aimed a systematic and detailed comparison of the SWD patterns of both strains in terms of the intensity, frequency and waveform morphology of the discharges by using exactly the same measurement and analysis techniques. The number, cumulative total duration and mean duration of SWDs were significantly higher in GAERS compared to WAG/Rij, while the discharge frequency was higher in the WAG/Rij. Furthermore, SWDs spectra and average SWD waveforms indicated that a single cycle of the SWD contains more energy in faster components such as spike and late positive transient in the GAERS. Additionally, WAG/Rij exhibited a significantly higher power between 8 and 14 Hz during the pre-SWD period. These clear phenomenological differences in the EEGs of both animal models suggest that these variables may represent basic phenotypic features of SWDs that should be sought after in the future studies that explore the genetic and molecular basis of absence epilepsy. (C) 2009 Elsevier B.V. All rights reserved.Publication Metadata only EFFECT OF METHYLENE-BLUE ON BLOOD-PRESSURE IN RATS(KARGER, 1993) ONAT, FİLİZ; OKTAY, S; ONAT, F; KARAHAN, F; ALICAN, I; OZKUTLU, U; YEGEN, BCMethylene blue (MB) is a soluble guanylate cyclase inhibitor, and known as an endothelium-derived relaxing factor (EDRF) inhibitor in vitro. In the present study, it was demonstrated that intravenous administration of MB caused a dose-dependent hypertensive effect in rats. The hypertensive responses to the higher doses (10 and 20 mg/kg) of MB was followed by a reflex hypotension which did not appear in pithed rats. Noradrenaline depletion by reserpine pretreatment did not inhibit MB-induced hypertension, but abolished the hypotensive response. Both hypertensive and hypotensive phases were not altered by indometacin. These results may suggest that in vivo guanylate cyclase inhibition leads to an increase in blood pressure; prostaglandins and noradrenaline release from sympathetic nerve endings do not contribute to MB-induced hypertension and it may be due in part to the inhibition of EDRF.Publication Metadata only The relationship between age-related development of spike-and-wave discharges and the resistance to amygdaloid kindling in rats with genetic absence epilepsy(ACADEMIC PRESS INC ELSEVIER SCIENCE, 2008) ONAT, FİLİZ; Carcak, Nihan; Aker, Rezzan Guelhan; Oezdemir, Osman; Demiralp, Tamer; Onat, Filiz YilmazGenetic Absence Epilepsy Rats from Strasbourg (GAERS) are resistant to amygdaloid kindling. Since in GAERS the characteristics of spike-and-wave discharges (SWDs) change with age, we have studied the relation between SWD maturation and the development of kindling resistance. Non-epileptic Wistar rats and GAERS were stimulated in basolateral amygdala with 400 mu A at 20 min intervals until they reached stage 5 seizures or for a maximum of 36 stimulations. All of the Wistar rats, the postnatal (PN) day 20 GAERS and the (kindling-prone) subgroups of GAERS at PN30 and PN60 reached stage 5 seizures; at PN20, PN30 and PN60 kindling rates were significantly slower in GAERS compared to Wistar rats. At PN30 and PN60, 41% and 69% of GAERS, respectively, showed no stage 3, 4 or 5 seizures after 36 stimulations (kindling-resistant subgroups). The SWD maturation involves changes in spectral patterns and correlate with age-related increases in kindling resistance in GAERS. (C) 2008 Elsevier Inc. All rights reserved.Publication Open Access Animal models of absence epilepsies: What do they model and do sex and sex hormones matter?(ACADEMIC PRESS INC ELSEVIER SCIENCE, 2014-12) ONAT, FİLİZ; van Luijtelaar, Gilles; Onat, Filiz Yilmaz; Gallagher, Martin J.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 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.Publication Metadata only ARE M-CHOLINOCEPTORS OF GUINEA-PIG GALLBLADDER SMOOTH-MUSCLE OF M4 SUBTYPE(KARGER, 1993) ONAT, FİLİZ; OZKUTLU, U; ALICAN, I; KARAHAN, F; ONAT, F; YEGEN, BC; ULUSOY, NB; OKTAY, SThe antagonism of carbachol-induced contractions of guinea pig gallbladder smooth muscle strips via selective antagonists, methoctramine, HHSiD, pf-HHSiD and DABDMA has been investigated in order to find out the m-cholinoceptor subtype(s) of gallbladder smooth muscle. All m-cholinoceptor antagonists examined, displaced the concentration-response curves to the right parallel in a concentration-dependent manner without affecting the maximum response. Schild analysis of data was consistent with competitive antagonism. -log K(B) values of the antagonists were 7.37 for HHSiD, 7.53 for pf-HHSiD, 6.58 for DABDMA and 7.60 for methoctramine. These results, together with the high affinity of pirenzepine and low affinities of 4-DAMP and AF-DX 116, indicate that the m-cholinoceptors of the guinea pig gallbladder which mediate cholinergic contractions are not of m1-, m2- and m3-subtypes but seem likely to be of m4-subtype.Publication Open Access The effects of partial bilateral lesioning of substantia nigra in a genetic absence epilepsy rat model(2002-04-01) GÜLHAN, REZZAN; ONAT, FİLİZ; GÖREN, MEHMET ZAFER; GÖREN M. Z., GÜLHAN R., ONAT F., Ergün A.Objective: \"Genetic Absence Epilepsy Rats from Strasbourg\" (GAERS), an inbred Wistar strain, serve as an experimental venue. These rats generate spontaneous spike-and-wave discharges (SWD) and have increased γ-aminobutyric acid (GABA) levels in the ventrolateral thalamus (VLT). Recently, substantia nigra pars reticulata (SNpr) was reported to act as an endogeneous inhibitory mechanism in the generation, onset and maintenance of various types of seizures. The presence of tonic control exerted by SNpr in absence seizures should also be tested in GAERS. Methods: In this current study, GABA and L-glutamic acid release in VLT of GAERS with partial bilateral electrolytic lesions of SNpr was evaluated by using microdialysis technique with fluorescent detection. Results: GABA levels in VLT were 0.12±0.04 μM and 0.24±0.08 μM in sham-lesioned and SNpr-lesioned GAERS, respectively. L-glutamic acid level was found to be 0.41 5±0.150 μM in sham-lesioned group and 0.324±0.094 μM in SNpr-lesioned GAERS. Statistical analysis revealed no significant difference between sham-lesioned and SNpr-lesioned rats. The number and the duration of SWD were also similar in two groups. Conclusion: These findings show that SNpr does not exert a tonic control in GAERS and we assume that intact SNpr acts as a site that may exert an inhibition on target structures when activated in GAERS.Publication Metadata only Seizure expression, behavior, and brain morphology differences in colonies of Genetic Absence Epilepsy Rats from Strasbourg(WILEY, 2014) ONAT, FİLİZ; Powell, Kim L.; Tang, Howard; Ng, Caroline; Guillemain, Isabelle; Dieuset, Gabriel; Dezsi, Gabi; Carcak, Nihan; Onat, Filiz; Martin, Benoit; O'Brien, Terence J.; Depaulis, Antoine; Jones, Nigel C.ObjectiveOriginally derived from a Wistar rat strain, a proportion of which displayed spontaneous absence-type seizures, Genetic Absence Epilepsy Rats from Strasbourg (GAERS) represent the most widely utilized animal model of genetic generalized epilepsy. Here we compare the seizure, behavioral, and brain morphometric characteristics of four main GAERS colonies that are being actively studied internationally: two from Melbourne (MELB and STRAS-MELB), one from Grenoble (GREN), and one from Istanbul (ISTAN). MethodsElectroencephalography (EEG) recordings, behavioral examinations, and structural magnetic resonance imaging (MRI) studies were conducted on GAERS and Non-Epileptic Control (NEC) rats to assess and compare the following: (1) characteristics of spike-and-wave discharges, (2) anxiety-like and depressive-like behaviors, and (3) MRI brain morphology of regions of interest. ResultsSeizure characteristics varied between the colonies, with MELB GAERS exhibiting the least severe epilepsy phenotype with respect to seizure frequency, and GREN GAERS exhibiting four times more seizures than MELB. MELB and STRAS-MELB colonies both displayed consistent anxiety and depressive-like behaviors relative to NEC. MELB and GREN GAERS showed similar changes in brain morphology, including increased whole brain volume and increased somatosensory cortical width. A previously identified mutation in the Cacna1h gene controlling the Ca(V)3.2 T-type calcium channel (R1584P) was present in all four GAERS colonies, but absent in all NEC rats. SignificanceThis study demonstrates differences in epilepsy severity between GAERS colonies that were derived from the same original colony in Strasbourg. This multi-institute study highlights the potential impact of environmental conditions and/or genetic drift on the severity of epileptic and behavioral phenotypes in rodent models of epilepsy.