Ebru Onalan

Serotonin transporter gene polymorphism implicates reduced orbito-frontal cortex in obsessive–compulsive disorder

Although a number of magnetic resonance imaging (MRI) and genetic studies have been performed on obsessive-compulsive disorder (OCD), only limited studies in which genetic and neuroanatomical variables are evaluated concurrently have been performed. Therefore, the aim of our present study is (to understand) better understanding how genetic variation in the promoter region of the 5-HTT gene (5-HTTLPR) is associated with key brain structures in OCD, orbito-frontal cortex (OFC), thalamus and anterior cingulate. 5-HTT genotypes (SS, SL, LL) were determined for 40 patients with OCD and the same number of healthy controls. MRI-derived volumes of the OFC, thalamus, and anterior cingulate were determined by reliable tracing techniques. Volumetric measurements were made with T1-weighted coronal MRI images, with 1.5-mm-thick slices, at 1.5T, and were done blindly. In comparison with controls, OCD patients demonstrated volumes reduction in OFC, increased volumes of thalamus and total white matter volumes, but no difference in total brain volume, total gray matter volumes and anterior cingulate volumes. No significant difference was observed in allelic frequencies between the patients and controls. The stronger effects of 5-HTT polymorphism on brain morphology in OCD than those in controls were determined in the both OFC and thalamus. On the other hand, for the OCD patients, ANCOVA revealed a significant main effect of genotype for both the OFC and thalamus and a significant genotype-by-side interaction for the OFC, demonstrating that the short variants had a smaller right OFC than the long variants. In conclusion, we found a significant genotype-diagnosis interaction effects on key brain structures, with a stronger effects of 5-HTT polymorphism in OFC and thalamus of OCD patients, whereas no morphological changes related to the polymorphism were found in normal individuals.

The association of myelin oligodendrocyte glycoprotein gene and white matter volume in obsessive–compulsive disorder

BACKGROUND Morphological changes of white matter have been described in patients with obsessive-compulsive disorder (OCD). The aim of our study was to determine whether a functional polymorphism of the myelin oligodendrocyte glycoprotein (MOG) G511C (Val142Leu) is associated with white matter volumes in patients with OCD. METHODS The MOG G511C (Val142Leu) genotypes (Val/Val, Val/Leu and Leu/Leu) were determined for 30 patients with OCD and the same number of healthy controls. Magnetic resonance imaging (MRI) scans were obtained and analyzed by the software program. RESULTS In comparison with controls, while no difference in total brain volume and total gray matter volumes was seen, total white matter volumes of the patients were larger than those of healthy controls. The genotypic pattern of distribution of MOG G511C was not different between the OCD patients and the controls. ANCOVA analysis in the OCD patients revealed a significantly larger total white matter volumes in patients carrying the MOG G511C (Val142Leu) Val/Val genotype compared with those carrying the Val/Leu and Leu/Leu genotypes. The analyses revealed no significant effects of genotype in the combined group but there was a statistically significant diagnosis effect, and an interaction between diagnosis and genotype effect. CONCLUSIONS Our study provides first evidence that the MOG G511C (Val142Leu) polymorphism might be associated with structural changes in the total white matter volumes of OCD patients, which might indicate an interaction between genetics and neuroimaging abnormalities in these patients.

Effects of central irisin administration on the uncoupling proteins in rat brain

Irisin is a thermogenic peptide that enables the development of brown adipose tissue from white adipose tissue by activating the UCP1. This study has been designed to determine the effects of the irisin on UCPs. Sprague Dawley female rats were used in the study. 1, 3 and 10μM concentrations of irisin were injected intracerebroventricularly to the rats, and the control group was received only vehicle. The animals were killed at the 16, 24, and 48h time intervals and their brains were taken out. The hypothalamus, pituitary gland, hippocampus, cerebellum, striatum and cortex areas were separated and the UCP2, UCP3, UCP4 and UCP5 mRNA levels were determined. Just before the animals were killed, their body temperatures were recorded. It was observed that after application of the high dose irisin, UCP5 mRNA level in the all brain areas increased (p<0.05); it was also observed that the three doses decreased the UCP4 expression in all brain areas (except the pituitary gland; p<0.05). The UCP2 and UCP3 mRNA expressions showed significantly increase in cerebellum and striatum (p<0.05). The UCP2 mRNA expression decreased in hypothalamus, pituitary gland, hippocampus and cortex areas (p<0.05). It was also observed that the body temperatures of the rats increased depending on the irisin injection and this increase was the most considerable at the 24h (p<0.05). The results of this study suggest that the UCP2-5 is expressed in different areas of the brain, and the irisin affects this expression, and may have effective roles in some brain functions.

Effects of apelin on reproductive functions: relationship with feeding behavior and energy metabolism

Abstract Apelin is an adipose tissue derived peptidergic hormone. In this study, 40 male Sprague–Dawley rats were used (four groups; n = 10). Apelin-13 at three different dosages (1, 5 and 50 μg/kg) was given intraperitoneally while the control group received vehicle the same route for a period of 14 days. In results, apelin-13 caused significant decreases in serum testosterone, luteinizing hormone and follicle-stimulating hormone levels (p < 0.05). Administration of apelin-13 significantly increased body weights, food intake, serum low-density lipoprotein and total cholesterol levels (p < 0.05), but caused significant decreases in high-density lipoprotein levels (p < 0.05). Serum glucose and triglyceride levels were not significantly altered by apelin-13 administration. Significant decreases in both uncoupling protein (UCP)-1 levels in the white and brown adipose tissues and UCP-3 levels in the biceps muscle (p < 0.05) were noted. The findings of the study suggest that apelin-13 may not only lead to obesity by increasing body weight but also cause infertility by suppressing reproductive hormones.

Potential role of melastatin-related transient receptor potential cation channel subfamily M gene expression in the pathogenesis of urinary bladder cancer

Urinary bladder cancer is one of the most common malignancies of the urinary tract. Ion channels and calcium homeostasis are involved in almost all basic cellular mechanisms. The transient receptor potential cation channel subfamily M (TRPM) takes its name from the melastatin protein, which is classified as potential tumor suppressor. To the best of our knowledge, there have been no previous studies in the literature investigating the role of these ion channels in bladder cancer. The present study aimed to determine whether bladder cancer is associated with mRNA expression levels of TRPM ion channel genes, and whether there is the potential to conduct further studies to establish novel treatment modalities. The present study included a total of 47 subjects, of whom 40 were bladder cancer patients and 7 were controls. Following the histopathological evaluation for bladder carcinoma, the mRNA and protein expression of TRPM were examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry in tumor and normal tissues, in order to determine whether there is a difference in the expression of these channels in tumor and normal tissues. Immunoreactivity for TRPM2, TRPM4, TRPM7 and TRPM8 was observed in epithelial bladder cells in the two groups. RT-qPCR revealed a significant increase in TRPM7 expression in bladder cancer tissue compared to the controls (healthy bladder tissue), whereas no differences in TRPM2 or TRPM4 expression levels were observed. There were significant reductions in the expression levels of TRPM5 and TRPM8 in bladder cancer tissues. In the present study, the effects of TRP ion channels on the formation of bladder cancer was investigated. This study is instructive for TRPM2, TRPM4, TRPM5, TRPM7 and TRPM8 and their therapeutic role in bladder cancer. The results support the fact that these gens can be novel targets and can also be tested for during the treatment of bladder cancer.

Central irisin administration suppresses thyroid hormone production but increases energy consumption in rats

Irisin, which is secreted from the skeletal muscle in response to physical exercise and defined as a thermogenic peptide, may play an important role in energy metabolism. Thyroid hormones, which are one of the other influential factors on the metabolic status, increase heat production and are the main regulators of energy metabolism. This study was conducted to determine the possible effects of irisin administration on thyroid hormones. Forty adult male Wistar albino rats were used in the study. The rats were equally divided into 4 groups (n = 10). The brain infusion kit was implanted in the groups, and irisin (or solvent as control) was centrally administered to the rats via osmotic mini pumps for 7 days. During the experiment, food consumption, body weights, and body temperatures of the animals were recorded. Food intake was significantly increased in the groups treated with irisin (p < 0.05), but their body weights were not changed. Hypothalamic TRH gene expression, serum TSH, fT3, and fT4 levels were significantly lower in the groups treated with irisin as compared to the naive and control groups (p < 0.05). In addition, irisin increased UCP1 mRNA expression in white and brown adipose tissue and UCP3 mRNA expression in muscle tissue in rats and also raised their body temperature (p < 0.05). Consequently, although central irisin administration has inhibitory effects on the hypothalamic-pituitary-thyroid axis, it seems to be an important agent in the regulation of food intake and energy metabolism.

Octreotide ameliorates dermal fibrosis in bleomycin-induced scleroderma

Background/aim Insulin-like growth factor (IGF)-I is a differentiation and growth factor. Antifibrotic action of octreotide has been reported in pulmonary fibrosis. The present study aimed to research the prophylactic and therapeutic potential of octreotide on a bleomycin (BLM)-induced experimental scleroderma model. Materials and methods Sixty Balb/c female mice were divided into 6 groups. Daily subcutaneous BLM (100 μg) was injected for 3 weeks in groups II and III and for 6 weeks in groups V and VI. Octreotide (100 μg/kg per day) was injected subcutaneously for the first 3 weeks in group III (prophylactic) and the second 3 weeks in group VI (therapeutic). Mice in groups I, II, and III were sacrificed at the end of the third week, while mice in groups IV, V, and VI were sacrificed at the end of the sixth week. Results Repeated BLM applications increased dermal inflammatory cell counts and dermal thickness, and led to dermal fibrosis at both the third and sixth weeks. Moreover, mRNA expressions of TGF-β1 and IGF binding protein (IGFBP)-3 and -5 were higher in the BLM- injected sham groups. On the other hand, IGFBP-3 and -5 mRNA expressions were significantly decreased in both the prophylactic and therapeutic octreotide groups. Similarly, octreotide decreased dermal inflammatory infiltrations and dermal thickness. Conclusion Octreotide has antifibrotic actions on experimentally induced dermal fibrosis. It can be suggested that IGF-I plays pathogenic roles, and octreotide is a candidate for research in the treatment of scleroderma.

Paricalcitol Inhibits Wnt/β-Catenin Signaling Pathway and Ameliorates Dermal Fibrosis in Bleomycin Induced Scleroderma Model

Objectives This study aims to determine the prophylactic and therapeutic efficacy of inhibition of Wnt/β-catenin signaling pathway with paricalcitol in an experimental scleroderma model created with bleomycin (BLM). Materials and methods Sixty female BALB/c mice (8-week old and weighing 25 g to 30 g) were divided into six groups as prophylactic-early [group 1 (control I)], sham I (group 2), paricalcitol I (group 3), therapeutic-late [group 4 (control II)], sham II (group 5), and paricalcitol II (group 6) groups. Subcutaneous BLM (100 μg/day) injections were used to induce dermal fibrosis and paricalcitol (0.3 μg/kg/day) was applied subcutaneously to BLM-injected mice during the first three weeks for preventive interventions and in the second three weeks for therapeutic interventions. Tissue samples were harvested for subsequent pathological and real-time polymerase chain reaction analysis. Tissue transforming growth factor-beta 1, axin-1, and Wnt-2 messenger ribonucleic acid expressions were determined by real-time polymerase chain reaction. Results Repeated BLM applications increased the dermal inflammatory cell infiltration and dermal thickness, and led to dermal fibrosis, in both early and late stages. Similarly, transforming growth factor-beta 1, axin-1, and Wnt-2 expressions were significantly increased in the sham groups compared to the own control group (p<0.05 for all). Contrarily, prophylactic and therapeutic paricalcitol applications decreased the transforming growth factor-beta 1, axin-1, and Wnt-2 messenger ribonucleic acid expressions compared to the own sham group (p<0.05 for all). In addition, the regressions in dermal necro-inflammation and dermal fibrosis on pathological views were also observed in the paricalcitol applied groups. Conclusion In this model, increased axin-1 and Wnt-2 messenger ribonucleic acid expressions suggest that Wnt/β-catenin pathway is active in dermal fibrosis.

Irisin levels increase during experimentally induced acute myocardial infarction

Background: Irisin is a hormone involved in energy metabolism. To date, however, there are scant data regarding irisin levels in infarcted tissues. Objective: To evaluate changes in irisin levels in the cardiac tissue of rats during experimentally induced myocardial infarction (MI). Methods: A total of 21 rats, comprising three groups of seven animals each (MI-1, MI-2 and a control group), were used. Isoproterenol (150 mg/kg once daily for two days ) was used to induce acute MI. The rats in the MI-1 group were evaluated at the end of the first week after the development of MI; rats in MI-2 were evaluated at the end of the second week after the development of MI. Following decapitation, irisin levels in the removed cardiac tissue were examined using polymerase chain reaction and immunohistochemical methods. Results : Following Masson trichrome stain, irisin levels were found to be increased in the cardiac tissue of MI-1 and MI-2 rats compared with the control group. Furthermore, polymerase chain reaction findings demonstrated that messenger RNA levels of irisin increased by a mean (± SD) factor of 23.3±0.2 in MI-1 rats and 15.9±0.3 in MI-2 rats compared with the control group (P=0.001 for both groups). In addition, immunohistochemical methods revealed that the strength and prevalence of irisin immunoreactivity displayed a significant increase in MI-1 rats (+3 strength) and MI-2 rats (+2 strength) compared with the control group (+1 strength) (P=0.01). Conclusion: The present study demonstrated an increase in irisin levels in the cardiac tissue of rats with experimentally induced MI. Further studies will determine the significance of this increase in the pathogenesis of MI.

AB0108 Resveratrol Inhibits Canonical Wnt Signaling and Ameliorates Experimental Arthritis

Background Rheumatoid arthritis (RA) is an inflammatory joint disorder, the progression of which leads to the destruction of cartilage and bone. Wnt signaling pathway act several important biological functions, such as cell differentiation, embryonic development, limb development and joint formation. Accumulated evidence has suggested that this signaling pathway plays a key role in the FLS activation, bone resorption and joint destruction in RA. Objectives The purpose of this study was to investigate the activity of Wnt/β-catenin pathway in collagen-induced arthritis (CIA) in rats, and to research the therapeutic effect of resveratrol in this arthritis model. Methods Thirty Wistar albino female rats were randomized to 3 groups (n=10 in each group): Group-I as the control group, Group-II as the arthritis (sham) group, and Group-III as the Resveratrol group. Arthritis was induced by intradermal injection of chicken type II collagen combined with incomplete Freunds adjuvant. One day after the onset of arthritis, resveratrol (20 mg/kg/day) was given via oral gavage, until they were killed on day 29. Animals were sacrificed at the 15th day after the onset of arthritis. The paws of the rats were obtained for further analysis. Perisynovial inflammation and cartilage-bone destruction were determined histopathologically in the paws. Tissue Wnt-5a, axin-2, DKK1, mitogen-activated protein kinase (MAPK), Src tyrosine kinase and signal transducer and activator of transcription-3 (STAT3) mRNA expressions were determined by real-time polymerase chain reaction (RT-PCR). Results Arthritis was clinically developed at 12 to 13 days after the injection of collagen (Fig. 1a). The 29th day scores were decreased in the paricalcitol and pyrvinium groups compared to the own 13th day score (p<0.05 for both), while it was increased in the sham group (p<0.05). Histopathological analysis demonstrated the extensive perisynovial inflammation and marked cartilage-bone destruction in sham group rats. Resveratrol treatment decreased the perisynovial inflammation and cartilage-bone destruction in the paws. Moreover, the tissue mRNA expressions of Wnt5a (11 folds), axin-2 (22 folds) and DKK1 (3 folds) were increased in the sham group compared to the control group (Fig. 1b-d). However, resveratrol treatment decreased their expressions.Figure 1. Assessments of daily arthritis score (a) and the tissue mRNA expressions of Wnt5 (b), axin 2 (c) and DKK1 (d) in the all study groups. Conclusions The present study shows that Wnt signaling pathway is active in CIA model. Resveratrol inhibits Wnt pathway and ameliorates CIA. References Zou Y, et al. Mol Med Rep. 2015;12(5):7221–6. Liu H, et al. Stem Cells Int. 2016;2016:2524092. Kotha A, et al. Mol Cancer Ther. 2006;5(3):621–9. Zhong LX, et al. J Ovarian Res. 2015;8:25. Acknowledgement None Disclosure of Interest None declared