Browsing by Author "Can, Gunes"

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Citation - WoS: 27
Citation - Scopus: 31
Dna Redox Modulations and Global Dna Methylation in Bipolar Disorder: Effects of Sex, Smoking and Illness State
(Elsevier Ireland Ltd, 2018) Ceylan, Deniz; Scola, Gustavo; Tunca, Zeliha; Isaacs-Trepanier, Cameron; Can, Gunes; Andreazza, Ana C.; Young, L. Trevor
DNA redox modulations and methylation have been associated with bipolar disorder (BD) pathophysiology. We aimed to investigate DNA redox modulation and global DNA methylation and demethylation levels in patients with BD during euthymia, mania or depression in comparison to non-psychiatric controls. The roles of sex and smoking as susceptibility factors for DNA redox modulations and global DNA methylation and demethylation were also explored. Levels of 5-methylcytosine (5-mC), 5-hydroxymethylcytosine (5-hmC) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were assessed in DNA samples of 75 patients with DSM-IV BD type I (37 euthymic, 18 manic, 20 depressive) in comparison to 60 non-psychiatric controls. Levels of 5-mC and 5-hmC were assessed using Dot Blot as a screening process, and verified using ELISA. Levels of 8-OHdG were assessed using ELISA. The levels of 8-OHdG significantly differed among non-psychiatric control, euthymia, mania and depression groups [F (3,110) = 2.771, p = 0.046], whereas there were no alterations in the levels of 5-hmC and 5-mC. Linear regression analyses revealed the significant effects of smoking (p = 0.031) and sex (p = 0.012) as well as state of illness on the levels of 8-OHdG (p = 0.025) in patients with BD. Our results suggest that levels of 8-OHdG may be affected by sex, illness states and smoking in BD.
Citation - WoS: 1
Increased Serum Levels of Nmda Receptor Antibodies in Female Patients With Bipolar Disorder
(Klinik Psikiyatri Dergisi, 2019) Ceylan, Deniz; Akan, Pinar; Doyuran, Kerim; Can, Gunes; Ersen, Ayca; Misir, Emre; Ozerdem, Aysegul
Objective: Glutamatergic/GABAergic imbalance due to autoimmune antibodies targeting N-methyl-D-aspartate receptors (NMDA-R) is considered to be one of the shared pathways between bipolar disorder (BD) and autoimmune diseases. Evidence shows female vulnerability to autoimmune disorders, and suggests a sex-specific approach in autoimmunity research in BD. We aimed to assess serum concentrations of NMDA-R antibodies and density of NMDA and GABA receptors on platelets in euthymic patients with BD in comparison to healthy individuals; and to determine the impact of sex on serum concentrations of NMDA-R antibodies and the density of NMDA and GABA receptors on platelets. Method: NMDA antibody IgG were detected in serum samples of 27 DSM IV euthymic patients with bipolar disorder (16 females, 11 males) and 33 healthy individuals (17 females, 16 males), using ELISA method. The densities of NMDA and GABA receptors on platelets were investigated using immunocytochemical methods. Results: Patients with BD presented higher serum levels of NMDA-R antibodies in comparison to healthy individuals (p < 0.001). The densities of NMDA and GABA receptor on platelets were similar in both groups. The NMDA-R antibody levels were influenced by both diagnosis and sex (F = 5.813, df = 1, p = 0.020). Tserum lithium levels showed a significant linear association with the serum NMDA-R antibody levels even adjusting for age, sex, body mass index (F = -56.26, t = -2.52, p = 0.015, CI: -101.12/-11.40). Discussion: Our findings support a potential role of NMDA-R antibodies in the underlying pathophysiology of BD, particularly for females.
Citation - WoS: 26
Citation - Scopus: 31
Oxidatively-Induced Dna Damage and Base Excision Repair in Euthymic Patients With Bipolar Disorder
(Elsevier Science Bv, 2018) Ceylan, Deniz; Tuna, Gamze; Kirkali, Guldal; Tunca, Zeliha; Can, Gunes; Arat, Hidayet Ece; Kant, Melis
Oxidatively-induced DNA damage has previously been associated with bipolar disorder. More recently, impairments in DNA repair mechanisms have also been reported. We aimed to investigate oxidatively-induced DNA lesions and expression of DNA glycosylases involved in base excision repair in euthymic patients with bipolar disorder compared to healthy individuals. DNA base lesions including both base and nucleoside modifications were measured using gas chromatography-tandem mass spectrometry and liquid chromatography-tandem mass spectrometry with isotope-dilution in DNA samples isolated from leukocytes of euthymic patients with bipolar disorder (n = 32) and healthy individuals (n = 51). The expression of DNA repair enzymes OGG1 and NEIL1 were measured using quantitative real-time polymerase chain reaction. The levels of malondialdehyde were measured using high performance liquid chromatography. Seven DNA base lesions in DNA of leukocytes of patients and healthy individuals were identified and quantified. Three of them had significantly elevated levels in bipolar patients when compared to healthy individuals. No elevation of lipid peroxidation marker malondialdehyde was observed. The level of OGG1 expression was significantly reduced in bipolar patients compared to healthy individuals, whereas the two groups exhibited similar levels of NEIL1 expression. Our results suggest that oxidatively-induced DNA damage occurs and base excision repair capacity may be decreased in bipolar patients when compared to healthy individuals. Measurement of oxidatively-induced DNA base lesions and the expression of DNA repair enzymes may be of great importance for large scale basic research and clinical studies of bipolar disorder.