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ONAT, FİLİZ

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ONAT

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FİLİZ

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Now showing 1 - 10 of 63
  • Publication
    Electroencephalographic differences between WAG/Rij and GAERS rat models of absence epilepsy
    (ELSEVIER, 2010) ONAT, FİLİZ; Akman, Ozlem; Demiralp, Tamer; Ates, Nurbay; Onat, Filiz Yilmaz
    The 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
    EFFECT OF METHYLENE-BLUE ON BLOOD-PRESSURE IN RATS
    (KARGER, 1993) ONAT, FİLİZ; OKTAY, S; ONAT, F; KARAHAN, F; ALICAN, I; OZKUTLU, U; YEGEN, BC
    Methylene 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
    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 Yilmaz
    Genetic 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
    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, S
    The 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
    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.
  • Publication
    EFFECTS OF KINDLING STIMULATIONS ON TYROSINE HYDROXYLASE IMMUNOREACTIVITY IN SUBSTANTIA NIGRA PARS RETICULATA OF GAERS AND WISTAR RATS
    (2013-06-27) GÜLÇEBİ İDRİZ OĞLU, MEDİNE; KARAMAHMUTOĞLU, TUĞBA; ONAT, FİLİZ; GÜLÇEBİ İDRİZ OĞLU M., AKMAN Ö., ÇARÇAK YILMAZ N., KARAMAHMUTOĞLU T., ONAT F.
  • Publication
    Electroencephalographic and behavioral effects of intracerebroventricular injection of grayanotoxin in adult Wistar rats
    (2011-08-28) KARAMAHMUTOĞLU, TUĞBA; GÜLÇEBİ İDRİZ OĞLU, MEDİNE; ONAT, FİLİZ; HALAÇ H. M. , TEMİZ G., KURU P., TORUN M., İSKENDER E., KARAMAHMUTOĞLU T., GÜLÇEBİ İDRİZ OĞLU M., ONAT F.
  • Publication
    Plasma lamotrigine levels of patients with polymorphic UGT1A4 enzymes
    (2010-06-27) GÜLÇEBİ İDRİZ OĞLU, MEDİNE; GÖREN, MEHMET ZAFER; GÜLHAN, REZZAN; ONAT, FİLİZ; GÜLÇEBİ İDRİZ OĞLU M., ÖZKAYNAKÇI A., GÖREN M. Z. , ÖZKARA Ç., GÜLHAN R., ONAT F.
  • Publication
    Suppressive effect of Rho-kinase inhibitors Y-27632 and fasudil on spike-and-wave discharges in genetic absence epilepsy rats from Strasbourg (GAERS)
    (SPRINGER, 2018) ONAT, FİLİZ; Carcak, Nihan; Yavuz, Melis; Karamahmutoglu, Tugba Eryigit; Kurt, Akif Hakan; Kucuk, Meral Urhan; Onat, Filiz Yilmaz; Buyukafsar, Kansu
    Rho/Rho-kinase (ROCK) signaling contributes to neuroinflammation, epileptogenesis, and seizures in convulsive-type epilepsies. However, this pathway has not been investigated in absence epilepsy. We investigated RhoA activity in genetic absence epilepsy rats from Strasburg (GAERS) and the effects of ROCK inhibitors Y-27632 and fasudil on spike-and-wave discharges (SWDs) of GAERS. ROCK level and activity were measured by Western blot analysis in the brain areas involved in absence seizures (i.e., cortex and thalamus) and hippocampus. Male GAERS were stereotaxically implanted with bilateral cortical electrodes for electroencephalogram (EEG) recordings and/or guide cannula into the right ventricle. ROCK inhibitors were administered by intraperitoneal injection (1-10mg/kg for Y-27632 or fasudil) or intracerebroventricular injection (7-20nmol/5l for Y-27632 or 10-100nmol/5l for fasudil). EEG was recorded under freely moving conditions. Compared with Wistar rats, GAERS exhibited increased RhoA activity in the somatosensory cortex but not in the thalamus or hippocampus. The single systemic administration of Y-27632 and fasudil partially suppressed the duration and frequency of absence seizure, respectively. However, local brain administration caused a widespread suppressive effect on the total seizure duration, number of seizures, and the average individual seizure length. In summary, Rho/ROCK signaling may be involved in the pathophysiology of absence epilepsy. Furthermore, ROCK inhibitors can control the expression of absence seizure in GAERS, thus indicating that Y-27632 and fasudil have the potential to be used as novel anti-absence drugs.
  • Publication
    Immunocytochemical analysis of glutamate and GABA in hippocampus of genetic absence epilepsy rats (GAERS)
    (2003) ONAT, FİLİZ; Sirvanci, Serap; Meshul, Charles K.; Onat, Filiz; San, Tangul
    In the present study, we used an immunocytochemical technique at the electron microscopic level to determine if there are changes in the glutamate and GABA neurotransmitter content of the hippocampus of genetic absence epilepsy rats from Strasbourg (GAERS). We also investigated if there was mossy fiber reorganization. After perfusion fixation, brains were removed and cryostat sections were stained according to the neo-Timm's procedure. High-resolution electron microscopy was used for ultrastructural examination of the hippocampus of GAERS and non-epileptic control Wistar animals. For ultrastructural and immunocytochemical studies, ultrathin-cut sections were obtained and immunolabeled with anti-glutamate and anti-GABA antibodies. The number of gold particles per nerve terminal was counted and the area of the nerve terminal was determined using the program NIH Image Analysis. No mossy fiber sprouting was detected in the hippocampus of GAERS. GABA and glutamate immunoreactivity were observed in the mossy fiber terminals of both the control and GAERS groups. Glutamate density in the CA3 region of GAERS hippocampus was found to be significantly increased compared to the control group. However, there was no difference in the GABA density of nerve terminals and in areas of GABAergic and mossy terminals between GAERS and the control group. The difference in glutamate level may merely be due to strain differences between the GAERS strain and the original Wistar strain or it is also possible that it appears after seizures have started.