Person: ÇAKIR, AYŞEN
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ÇAKIR
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AYŞEN
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Publication Anti-apoptotic and anti-oxidant effects of systemic uridine treatment in an experimental model of sciatic nerve injury(Türk Nöroloji Derneği, 2021-01-01) Khezri, Marzieh Karimi; Turkkan, Alper; Khezri, Marzieh Karimi; Koç, Cansu; KOÇ, CANSU; Salman, Berna; SALMAN, BERNA; Levent, Pinar; Cakir, Aysen; Kafa, Ilker Mustafa; Cansev, Mehmet; Bekar, Ahmet; ÇAKIR, AYŞEN; KAFA, İLKER MUSTAFA; CANSEV, MEHMET; BEKAR, AHMET; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Farmakoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Anatomi Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Fizyoloji Anabilim Dalı.; 0000-0002-6097-5585; 0000-0001-8309-0934; 0000-0003-2918-5064; AAA-4754-2022; ABX-9081-2022; A-6819-2018AIM: To investigate the anti-apoptotic and anti-oxidant effects of systemic uridine treatment in a rat model of sciatic nerve injury.MATERIAL and METHODS: Thirty-two adult male rats were equally randomized to Sham, Control, U100, and U500 groups. Sham rats received a sham operation by exposing the right sciatic nerve without transection, while those in the Control, U100, and U500 groups underwent right sciatic nerve transection followed by immediate primary anostomosis. Sham and Control groups received saline (0.9% NaCl) injections intraperitoneally (i.p.), while U100 and U500 groups received 100 mg/kg and 500 mg/kg uridine injections (i.p.), respectively, once a day for 7 days after the surgery. Rats in all the groups were sacrificed on the eighth day; sciatic nerve samples were analyzed for apoptosis by Western Blotting and for oxidation parameters including myeloperoxidase (MPO), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) by Enzyme-Linked Immunosorbent Assay (ELISA).RESULTS: Uridine treatment at the dose of 500 mg/kg significantly decreased as apoptosis determined by Caspase-3/Actin ratio and exhibited significant anti-oxidant effects as determined by decreased levels of MPO and MDA as well as increased levels of SOD, GPx, and CAT compared to controls. Uridine at 100 mg/kg was only found to decrease the Caspase-3/Actin ratio, although it significantly decreased MDA and increased CAT levels compared to controls.CONCLUSION: Treatment with uridine reduces apoptosis and oxidation in a rat model of sciatic nerve injury dose-dependently. Thus, uridine may be beneficial in peripheral nerve regeneration by exhibiting anti-apoptotic and anti-oxidant effects.Publication Antioxidative effects of uridine in a neonatal rat model of hyperoxic brain injury(TÜBİTAK, 2020-05-31) Al, Nevin; Çakir, Aysen; Koç, Cansu; Cansev, Mehmet; Alkan, Tülin; ÇAKIR, AYŞEN; KOÇ, CANSU; CANSEV, MEHMET; ALKAN, TÜLİN; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Fizyoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Farmakoloji Anabilim Dalı.; 0000-0002-6097-5585; 0000-0003-2918-5064; 0000-0001-6466-5042; AAA-4754-2022; A-6819-2018; M-9071-2019; AAH-1792-2021Background/aim: Premature birth is a major problem that results in an increased risk of mortality and morbidity. The management of such infants consists of supraphysiological oxygen therapy, which affects brain development due, in part, to the deterioration caused by reactive oxygen species (ROS). We showed previously that exogenously administered uridine provides neuroprotection in a neonatal rat model of hyperoxic brain injury. Hence, the aim of the present study was to investigate the effects of uridine on ROS in the same setting.Materials and methods: Hyperoxic brain injury was induced by subjecting a total of 53 six-day-old rat pups to 80% oxygen (the hyperoxia group) for a period of 48 h. The pups in the normoxia group continued breathing room air (21% oxygen). Normoxia + saline or hyperoxia + saline or hyperoxia + uridine 100 mg/kg or hyperoxia + uridine 300 mg/kg or hyperoxia + uridine 500 mg/kg was injected intraperitoneally (i. p.) 15 min prior to the hyperoxia procedure. The pups were decapitated and the brains were homogenized to analyze superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), myeloperoxidase (MPO), and malondialdehyde (MDA) enzymes as well as DJ-1 (protein deglycase DJ-1) - an oxidative stress-sensitive protein.Results: Hyperoxia-induced may cause overproduction of oxygen radicals and the oxidant/antioxidant balance may be disturbed in the brain. Brain MPO and MDA levels were significantly increased in saline-receiving pups exposed to hyperoxia. Brain SOD and GSH-Px levels were significantly decreased in saline-receiving pups exposed to hyperoxia. Our results showed that uridine administration prevented the hyperoxia-induced decrease in SOD and GSH-Px while counteracting the hyperoxia-induced increase in MPO and MDA in a dose-dependent manner. Uridine also increased the DJ-1 levels in brains of rat pups subjected to hyperoxia.Conclusion: These data suggest that uridine exhibits antioxidative properties which may mediate the protective effects of uridine in a neonatal rat model of hyperoxic brain injury.Publication Proteomics analysis of CA1 region of the hippocampus in pre-, progression and pathological stages in a mouse model of the alzheimer's disease(Bentham Science, 2019-01-01) Gürel, Buşra; Cansev, Mehmet; Koç, Cansu; Öçalan, Buşra; Çakır, Ayşen; Aydın, Samı; Kahveci, Nevzat; Ulus, İsmail Hakkı; Şahin, Betül; Başar, Merve Karayel; Baykal, Ahmct Tarık; CANSEV, MEHMET; KOÇ, CANSU; Öçalan, Buşra; ÇAKIR, AYŞEN; Aydın, Sami; KAHVECİ, NEVZAT; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Farmakoloji Bilim Dalı; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Fizyoloji Bilim Dalı; 0000-0002-6097-5585; 0000-0003-0841-8201; 0000-0002-3405-3640; 0000-0001-7729-7373; AAG-7070-2021; AAA-4754-2022; A-6819-2018; AAL-1786-2020; M-9071-2019; N-9927-2019; CCT-7508-2022Background: CA1 subregion of the hippocampal formation is one of the primarily affected structures in AD, yet not much is known about proteome alterations in the extracellular milieu of this region. Objective: In this study, we aimed to identify the protein expression alterations throughout the pre-pathological, progression and pathological stages of AD mouse model.Methods: The CA1 region perfusates were collected by in-vivo intracerebral push-pull perfusion from transgenic 5XFAD mice and their non-transgenic littermates at 3, 6 and 12 were beta months of age. Morris water maze test and immunohistochemistry staining of A performed to determine the stages of the disease in this mouse model. The protein expression differences were analyzed by label-free shotgun proteomics analysis.Results: A total of 251, 213 and 238 proteins were identified in samples obtained from CA1 regions of mice at 3, 6 and 12 months of age, respectively. Of these, 68, 41 and 33 proteins showed statistical significance. Pathway analysis based on the unique and common proteins within the groups revealed that several pathways are dysregulated during different stages of AD. The alterations in glucose and lipid metabolisms respectively in pre-pathologic and progression stages of the disease, lead to imbalances in ROS production via diminished SOD level and impairment of neuronal integrity.Conclusion: We conclude that CA1 region-specific proteomic analysis of hippocampal degeneration may be useful in identifying the earliest as well as progressional changes that are associated with Alzheimer's disease.Publication The effect of uridine on inflammatory mediators in rem sleep deprived rats(Wiley, 2023-01-01) Esmerce, Büşra Öcalan; Çakır, Aysen; Çilingir, Sümeyye; Suyen, Güldal; Kahveci, Nevzat; Esmerce, Büşra Öcalan; ÇAKIR, AYŞEN; KAHVECİ, NEVZAT; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Fizyoloji Anabilim Dalı.; 0000-0001-7729-7373; HMR-2796-2023; A-6819-2018; AAG-7070-2021Publication Uridine treatment improves nerve regeneration and functional recovery in a rat model of sciatic nerve injury(Turkish Neurosurgical Soc, 2022-01-01) Khezri, Marzieh Karimi; Türkkan, Alper; KOÇ, CANSU; Salman, Berna; SALMAN, BERNA; Levent, Pınar; Çakır, Aysen; ÇAKIR, AYŞEN; CANSEV, MEHMET; KAFA, İLKER MUSTAFA; Bekar, Ahmet; BEKAR, AHMET; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Anatomi Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Farmaoloji Anabilim Dalı.; 0000-0002-6097-5585; 0000-0001-8309-0934; 0000-0003-2918-5064; A-6819-2018; ABX-9081-2022AIM: To investigate the regenerative potential and long-term functional effects of uridine treatment in a rat model of sciatic nerve injury.MATERIAL and METHODS: Male Sprague-Dawley rats were randomized to receive sham surgery plus saline (Sham group), right sciatic nerve transection and primary repair plus saline (Control group), right sciatic nerve transection, and primary repair plus 500 mg/kg uridine (Uridine group). Saline or uridine was injected intraperitoneally (i.p.) for seven days, and the rats were monitored for 12 weeks after surgery. We evaluated electrophysiological and functional recovery using electromyography (EMG) and sciatic functional index (SFI) at six and 12 weeks, respectively. At 12 weeks, rats were decapitated and their right sciatic nerves were examined in macroscopic and histomorphologic manners.RESULTS: Functional evaluation by SFI and sciatic nerve conduction velocity analyzed by EMG both decreased in the Control group but recovered in the Uridine group 12 weeks after surgery. Additionally, upon experiment completion, Uridine treatment was observed to enhance nerve adherence, separability scores, and the number of myelinated axons.CONCLUSION: These results reveal that short-term Uridine treatment provides morphological and electrophysiological benefits, which are represented by long-term functional improvement in a rat model of sciatic nerve injury. These findings validate and extend our knowledge on Uridine's regenerative effects in peripheral nerve injuries.Publication The effect of cdp-choline on hippocampal tcamkii, pcamkii and pcreb levels in rem-sleep deprived rats(Wiley, 2019-12-01) Süyen, Güldal; Çakır, Aysen; ÇAKIR, AYŞEN; CANSEV, MEHMET; Öcalan, Buşra; Koç, Cansu; KOÇ, CANSU; KAHVECİ, NEVZAT; Kahveci, Nevzat; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Farmakoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Fizyoloji Anabilim Dalı.; 0000-0002-6097-5585; 0000-0003-2918-5064; 0000-0003-0841-8201; AAA-4754-2022; A-6819-2018; M-9071-2019; AAG-7070-2021Publication Melatonin treatment affects leptin and nesfatin-1 levels but not orexin-a levels in rem sleep deprived rats(Kafkas Univ, Veteriner Fakultesi Dergisi, 2023-09-01) Çakır, Aysen; ÇAKIR, AYŞEN; Sehzade, Sevda; Koç, Cansu; KOÇ, CANSU; Kahveci, Nevzat; KAHVECİ, NEVZAT; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Fizyoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Farmakoloji Anabilim Dalı.; 0000-0002-6097-5585Sleep contributes to the energy balance of body. This study aims to investigate how rapid eye movement (REM) sleep deprivation (SD) or recovery sleep affects rat weight and the serum levels of Nesfatin-1, Orexin-A, and Leptin; additionally, seeks to determine the impact of melatonin administration on these parameters. Male, Sprague Dawley rats were randomized into two groups (n=9). REMSD was induced using the modified multiple platform method (MMPM). Melatonin was used as a treatment (20 mg/kg). Study Group I was created to investigate the effectiveness of the treatment during REMSD. Study Group II was established to analyze the possible therapeutic role of melatonin and recovery sleep after REMSD-induced damage. The rats' weights were recorded during the experiments. Blood samples were collected from all rats via decapitation after experiments. The levels of serum Nesfatin-1, Orexin-A, and Leptin were analyzed using the ELISA method. REMSD affected weight of the rats and altered the levels of serum Nesfatin-1 and Leptin. Melatonin administration influenced weight gain and affected Nesfatin-1 and Leptin levels. REMSD or melatonin did not affect Orexin-A levels. REMSD and melatonin play significant roles in the body's energy balance. This study will contribute to elucidating the role of SD in metabolic processes and will play a role in assessing the impact of melatonin, a commonly used treatment in human and veterinary medicine.