Person: GÖREN, MEHMET ZAFER
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GÖREN
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MEHMET ZAFER
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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 Evaluation of the Effect of Prazosin Treatment on alpha-2c Adrenoceptor and Apoptosis Protein Levels in the Predator Scent-Induced Rat Model of Post-Traumatic Stress Disorder(HUMANA PRESS INC, 2020) GÖREN, MEHMET ZAFER; Aykac, Asli; Sehirli, Ahmet Ozer; Goren, M. ZaferThe predator scent-induced (PSI) stress model is a rat model used to mimic post-traumatic stress disorder (PTSD) symptoms in humans. There is growing evidence that prazosin, which blocks alpha-1 and is approved by the FDA as an anti-hypertensive drug, can potentially be of use in the treatment of PTSD-related sleep disorders. The aim of this study was to investigate the role of prazosin treatment on behavioral parameters (freezing time, total transitions, and rearing frequency measured from the open field; anxiety index, total entries and time spent in open arms calculated from the elevated plus maze), apoptotic proteins and alpha-2c-AR in fear memory reconsolidation in the PSI stress rat model. We used western blot analysis to determine the effect of prazosin (0.5 mg/kg/ip) on alpha-2c-AR and apoptotic protein expression changes in the frontal cortex, hippocampus, and amygdala. It was determined that in the stress group, there was increased freezing time and anxiety index, and decreased rearing frequency, total transitions, total entries, and time spent in open arms compared to the control groups. Following PSI-stress, pro-apoptotic (bax) protein expression levels increased and alpha-2c AR and anti-apoptotic protein (bcl-2) levels decreased in investigated all brain regions. The majority of stress-induced changes were recovered with prazosin treatment. The results of our study may potentially be useful in understanding the effect of prazosin treatment, given the fact that the amygdala, frontal cortex, and hippocampus regions are affected for stress conditions.Publication Metadata only Kokain(Akademisyen Kitabevi, 2021-01-01) GÖREN, MEHMET ZAFER; TIPLAMAZ S., GÖREN M. Z.Publication Metadata only 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 Open Access The α2C-adrenoceptor antagonist JP-1302 controls behavioral parameters, tyrosine hydroxylase activity and receptor expression in a rat model of ketamine-induced schizophrenia-like deficits(2022-11-01) AKAKIN, DİLEK; GÖREN, MEHMET ZAFER; Tekin N., Karamahmutoğlu T. E. , Aykaç A., AKAKIN D., GÖREN M. Z.© 2022Schizophrenia is a chronic disabling disease affecting 1 % of the population. Current antipsychotics have limited efficacy in mitigating the severity of the symptoms of the disease. Therefore, searching for new therapeutic targets is essential. Previous studies have shown that α2C-adrenoceptor antagonists may have antipsychotic and pro-cognitive effects. Therefore, the current study evaluates the behavioral and neurochemical effects of JP-1302, a selective α2C-adrenoceptor antagonist, in a model of schizophrenia-like deficits induced by sub-chronic ketamine (KET) administration. Here, we administered ketamine (25 mg/kg, i.p.) to male and female Wistar rats for eight consecutive days. On the last two days of ketamine administration, rats were pretreated with either JP-1302 (1-3-10 μmol/kg, i.p.), chlorpromazine (0.1 mg/kg, i.p.), or saline, and the behavioral tests were performed. Behaviors related to positive (locomotor activity), negative (social interaction), and cognitive (novel object recognition) symptoms of schizophrenia were assessed. Glutamate, glutamine, GABA levels, and α2C-adrenoceptor expression were measured in the frontal cortex and the hippocampus. Tyrosine hydroxylase immunocytochemical reactivity was also shown in the midbrain regions. Sub-chronic ketamine administration increased locomotor activity and produced robust social interaction and object recognition deficits, and JP-1302 significantly ameliorated ketamine-induced cognitive deficits. Ketamine induced a hyperdopaminergic activity in the striatum, which was reversed by the treatment with JP-1302. Also, the α2C-adrenoceptor expression was higher in the frontal cortex and hippocampus in the ketamine-treated rats. Our findings confirm that α2C-adrenoceptor antagonism may be a potential drug target for treating cognitive disorders related to schizophrenia.Publication Metadata only The relationship between UGT1A4 polymorphism and serum concentration of lamotrigine in patients with epilepsy(ELSEVIER, 2011) ONAT, FİLİZ; Gulcebi, Medine Idrizoglu; Ozkaynakci, Aydan; Goren, Mehmet Zafer; Aker, Rezzan Gulhan; Ozkara, Cigdem; Onat, Filiz YilmazLamotrigine (LTG) which has a widespread use in epilepsy treatment as an antiepileptic agent is metabolized by UDP-glucuronosyl transferase (UGT) enzymes. In this study, single nucleotide polymorphisms, P24T and L48V, of the UGT1A4 enzyme have been investigated in a Turkish population of patients with epilepsy (n=131) by comparing serum levels of LTG of wild type and polymorphic subjects. High performance liquid chromatography (HPLC) was used to measure serum concentrations of LTG. The P24T and L48V polymorphisms of the UGT1A4 enzyme were analyzed with a matrix assisted laser desorption-time of flight (MALDI-TOF) mass spectrometry method. The frequencies of the heterozygous alleles for L48V or P24T polymorphisms were 22.4% and 3.8%, respectively. L48V polymorphism was found to decrease the serum concentration of LTG in patients on monotherapy or polytherapy. The LTG levels of non smoking monotherapy patients were 52% lower for the L48V polymorphism than for wild type alleles. Also the LTG levels were significantly lower for non smoking or smoking polymorphic alleles than for normal. The high frequency of the L48V polymorphism detected in the Turkish population indicates that LTG dose adjustments in patients with the UGT1A4 L48V polymorphic enzyme should be taken into account. (c) 2011 Elsevier B.V. All rights reserved.Publication Open Access Plasma concentration-time profile of a single dose of enteric-coated omeprazole in male and female healthy volunteers(2000-01-01) GÖREN, MEHMET ZAFER; AKIN, ŞEHNAZ; GÜLHAN, REZZAN; ONAT, FİLİZ; Iskender E., ASLAN N., GÖREN M. Z., Tellioglu T., Akin S., Erin N., GÜLHAN R., ONAT F., Berkman K., Oktay S.O b je c tiv e : T h e b io a vaila b ility of a single dose (20 m g) o f tw o e n te ric -c o a te d o m e p ra z o le fo rm u la tio n s, m arketed in T urkey, given 10-15 m in b e fo re b reakfast, w as studied in 12 healthy vo lu n te e rs (6 m ales and 6 fem ales) in a d o u b le blind, cro s s o v e r design. M e th o d s : B lood sam ples w ere collected prior to and at 10 tim e points w ithin 12 hrs. after dosing. P la s m a o m e p ra z o le c o n c e n tra tio n s w e re m easured by H P LC te ch n iq u e in our laboratory. R e s u lts a n d C o n c lu s io n s : T he tw o products w ere found to be b io e q u iva le n t in term s of extent of a b s o rp tio n (th e a re a u n d e r the p la s m a c o n c e n tra tio n -tim e cu rve s). M u ltip e a k p la sm a co n ce n tra tio n pro file s w e re seen in m ost of the su b je cts w ith both products. T im e to the e a rlie r peaks w as 1-2 hrs. and those peaks w ere low er in a m p litu d e th a n th e p e a ks re a ch e d a p p ro x im a te ly 4 .5 hrs. a fte r the a p p lica tio n . In te re stin g ly, the m u ltip e a k profile w as m ore fre q u e n t and the e a rlie r peaks w ere sig nificantly higher in fe m a le su b je cts than in m ales. The reason fo r th is g e n d e r d iffe re n ce in m ultipeak p la s m a c o n c e n tra tio n - tim e p ro file of oral o m e p ra zo le needs fu rth e r investigation.Publication Open Access The behavioral and neurochemical effects of methylprednisolone or metyrapone in a post-traumatic stress disorder rat model(KARE PUBL, 2019) AYDIN OMAY, BANU; Tanriverdi, Ayse Melek; Aydin, Banu; Bebitoglu, Berna Terzioglu; Cabadak, Hulya; Goren, M. ZaferOBJECTIVE: Mechanisms contributing to the post-traumatic stress disorder (PTSD) that involve several physiological sys- tems, and the activation of the hypothalamic-pituitary-adrenal axis (HPA) is one of the most known systems in the PTSD pathophysiology. The present study investigates the potential effects of methylprednisolone, metyrapone and their association with the noradrenergic system within the rostral pons, a region containing the locus coeruleus (LC) in a rat model of PTSD induced with predator scent. METHODS: In this study, Sprague-Dawley rats were exposed to the stress by exposure to the scent of dirty cat litter, which is a natural stressor of a predator. One week later, the rats were re-exposed to a situational reminder (clean cat litter). The rats were treated using either methylprednisolone, metyrapone or physiological saline before exposure to a situational reminder (n=8 in each group). Noradrenaline (NA) levels in the rostral pons homogenates were analysed using ELISA. RESULTS: The anxiety indices of the rats exposed to the trauma were found to be significantly higher than the anxiety indices of the control rats. Metyrapone produced a significant increase in the anxiety indices of the non-stressed rats, and methylprednisolone did not produce a change in the anxiety indices of the non-stressed rats. Methylprednisolone treatment suppressed the anxiety in the stressed rats. Metyrapone treatment increased the anxiety indices in the stressed rats but still being lower than that of the saline-treated stressed rats. Significant decrease in the freezing time was observed following the methylprednisolone treatment both in the stressed and non-stressed rats. NA content in the rostral pons of the stressed rats was significantly higher than that of the non-stressed rats. Methylprednisolone or metyrapone treatments decreased the NA content in the non-stressed rats as compared to the saline treatment. However, these decreases were not significant. CONCLUSION: In this study, findings suggest that stress may give rise to endocrine, autonomic and behavioural responses. The anxiety indices and NA levels in the rostral pons increased with the traumatic event. The methylprednisolone treatment may suppress anxiety through interactions between the LC and the HPA axis.Publication Metadata only The change in plasma GABA, glutamine and glutamate levels in fluoxetine- or S-citalopram-treated female patients with major depression(SPRINGER HEIDELBERG, 2009) GÖREN, MEHMET ZAFER; Kucukibrahimoglu, Esra; Saygin, Melek Z.; Caliskan, Mecit; Kaplan, Okan K.; Unsal, Cuneyt; Goren, M. ZaferObjective The aim of this study was to investigate the relationship between plasma glutamate, glutamine and gamma-aminobutyric acid (GABA) levels in female patients with major depression treated with S-citalopram or fluoxetine. Methods The patients were assigned into S-citalopram (10 mg/day) or fluoxetine (20 mg/day) groups (n= 15 per group). The Hamilton and Beck Depression Inventory Scales were performed on all study participants, and blood samples were collected. The same procedures were repeated 10 days following the onset of therapy. Fifteen female healthy volunteers were also included in the study for the evaluation of normal plasma levels. Results The plasma GABA levels of the healthy volunteers were higher whereas those for glutamate and glutamine were lower than the day zero samples of the patients. An increase in plasma GABA levels and a decrease in glutamate and glutamine levels were observed on the 10th day of treatment. No difference was detected between the drug treatments. Conclusion Our findings may suggest that GABA, glutamate and glutamine play a role in depression and that plasma GABA may be used as a biomarker for treatment control.Publication Metadata only Kokain(Akademisyen Yayınevi Kitabevi, 2021-09-01) GÖREN, MEHMET ZAFER; Gören M. Z.