Browsing by Subject "nervous system development"
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Item The Effects of Methotrexate on the Development of Neural Tube Defects in the Chick Embryo(2003) Vatansever H.S.; Umur A.Ş.; Inan V.S.; Selçuki M.During chick development, one of the earliest differentiated tissues is the neural tube. After 24 h of incubation, a chick egg starts to differentiate and 30-48 h after incubation the neural plate is closed from head to tail to form the neural tube. If factors controlling the neural tube's closing are disrupted, this consequently causes neural tube closure defects during this time. In this study, the effect of methotrexate on the developing neural tube was investigated during early chick development. For this research, 40 specific pathogen free (SPF) white Leghorn type chick embryos were used. They were incubated for 30 h at 37.8 ± 2°C. Methotrexate, which inhibits the dihydrofolate reductase enzyme by a competitive mechanism, was injected within therapeutic dosage limits (10 mg/m2, 20 mg/m2, 40 mg/m2) in ovo. Ten eggs were injected with 0.9% NaCl and used as a control group. All groups, after the injection, were incubated for 48 and 72 h. They were then dissected and the embryos were fixed in 10% (v/v) formalin for 2 h. The embryos were embedded in paraffin wax and 5 μ serial sections were taken. Sections were stained with haematoxylin and then observed under light microscopy. While 20 mg/m2 or 40 mg/m2 methotrexate embryos were not alive when they were opened at 48 h incubation, 10 mg/m 2 methotrexate embryos maintained normal development after 48 and 72 h incubation. However, there was developmental retardation in the methotrexate injected group when compared with the control group with development of the brain being retarded; the volume of brain vesicles was lower than in the control group. Our results suggested that methotrexate, an antimetabolite of folic acid, caused neural tube closure defects when injected at therapeutic dosage levels. Folic acid is essential for normal development of the nervous system; therefore, folate antagonists might be more harmful to the central nervous system than to other parts of the developing body.Item Neural tissue continues its maturation at the site of neural tube closure defects: Implications for prenatal intervention in human samples(2004) Selçuki M.; Vatansever S.; Inan S.; Sanci M.; Sayhan S.; Baǧdatoǧlu C.Objective: Our objective was to investigate the relation between the embryological development and neural tissue maturation at the site where the neural plate failed to form a neural tube. Material and methods: Samples from 15 aborted human fetuses with neural tube defects (NTD). All of the fetuses were between 20 and 25 gestational weeks old. Indicators of neural tissue maturation, formation of basal lamina, expression of integrins and neuron specific class III beta tubulin (tuj1) were investigated. To detect the adverse effects of the environment, if any, p53 and bcl-2 activity at both sites of the open and closed neural plate were investigated as well. Results: No difference was found in the expression of maturation-related molecules at the site of the neural plate that remained open compared with the site where the neural tube is normally formed. While high p53 activity was noted in neural tissue at the site of the neural tube defect, no such activity was detected in the neural tissue where the neural tube is normally formed. Conclusion: Our results suggested that maturation and differentiation of neural tissue continued regardless of the failure of neural tube closure. Therefore, the neurological deficits that are encountered in NTD patients should be related to secondary damage such as amnion fluid toxicity, uterus contractions, labor, etc. It seems valuable to save the neural plate before the negative effects of the environment renders the neural tissue functionless. © Springer-Verlag 2004.Item Apoptosis seems to be the major process while surface and neural ectodermal layers detach during neurulation(2008) Selçuki M.; Vatansever S.; Umur A.S.; Temiz C.; Sayin M.Objective: The aim of this study is to demonstrate the process of detaching neural and surface ectodermal layers soon after the neurulation completes. Materials and methods: Specific pathogen-free chicken egg embryos were used to investigate the neurulation procedure. Ten eggs were saved as controls. The other ten eggs were opened at the 30th hour of embryo development and cultured with Z-VAD-FMK (peptide caspase inhibitor) to investigate the results of the apoptosis inhibition. Embryos were placed and developed up to 48 h in the culture medium. To detect apoptotic cells between neural and surface dermal layers, immunoreactivity of p53 and terminal uridine deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay were used. Results: While the control group shows positive immunoreactivity of p53 and TUNEL-positive apoptotic cells at the site where the neural folds detach from the surface ectoderm, no TUNEL activity and no detachment were detected in the apoptosis-inhibited group. Conclusion: As inhibition of apoptosis prevented the detachment of the neural and surface ectodermal layers from each other at the end of the neurulation, inhibition of apoptosis seemed to cause a considerable embryological error accounted for congenital dermal sinus tractus maldevelopment. © Springer-Verlag 2007.Item Correlation of serum BDNF levels with hippocampal volumes in first episode, medication-free depressed patients(2010) Eker C.; Kitis O.; Taneli F.; Eker O.D.; Ozan E.; Yucel K.; Coburn K.; Gonul A.S.The hippocampus seems to be affected in MDD, and brain-derived neurotrophic factor (BDNF) has positive effects on neurogenesis within the hippocampus. Although there are inconsistencies among study results, a smaller hippocampal volume in depressed patients is thought to be related to the pathophysiology of the disease. We looked at the correlation between serum BDNF (sBDNF) levels and hippocampal volumes (HCV) of first-episode MDD patients (18 female, 7 male; mean age = 32.1 ± 9.3) and healthy controls (17 female, 5 male; mean age = 29.7 ± 6.4). Region of interest analysis was conducted on the images acquired via MRI. sBDNF levels and HCV correlated only in the MDD group (right: r = 0.46, P = 0.02; left: r = 0.47, P = 0.02); however, HCV did not differ between MDD patients and healthy controls (right: F = 2.45, df = 1.46, P > 0.05; left: F = 0.05, df = 1.46, P > 0.05). BDNF may be a factor underlying HCV differences between MDD and healthy control subjects, which become apparent as severe and multiple episodes are experienced. © 2010 Springer-Verlag.Item Pregnancy outcomes following the use of thiocolchicoside(Elsevier Inc., 2016) Ozturk Z.; Olmez E.; Gurpinar T.; Vural K.Thiocolchicoside is a commonly used muscle relaxant in orthopedic, rheumatologic or musculoskeletal disorders to treat painful muscle spasms. It is contraindicated in pregnancy and lactation. There is no previously published experience with thiocolchicoside exposure during pregnancy. In this observational study, we collected and evaluated 18 pregnancy outcomes of the women referred to our prenatal consultation service for thiocolchicoside exposure between 2007-2012, and offspring were followed up until 2 years of age. There were 16 live births, 1 spontaneous abortion and 1 elective termination of pregnancy. No major birth defect was observed. The mothers and their babies were free of perinatal complications. No growth or developmental abnormalities were found during follow-up period. Our findings add information on inadvertent use of thiocolchicoside in pregnancy. Further large prospective cohort studies are required to investigate this issue. © 2016 Elsevier Inc.Item Neural correlates of implicit agency during the transition from adolescence to adulthood: An ERP study(Elsevier Ltd, 2021) Aytemur A.; Lee K.-H.; Levita L.Sense of agency (SoA), the experience of being in control of our voluntary actions and their outcomes, is a key feature of normal human experience. Frontoparietal brain circuits associated with SoA undergo a major maturational process during adolescence. To examine whether this translates to neurodevelopmental changes in agency experience, we investigated two key neural processes associated with SoA, the activity that is leading to voluntary action (Readiness Potential) and the activity that is associated with the action outcome processing (attenuation of auditory N1 and P2 event related potentials, ERPs) in mid-adolescents (13–14), late-adolescents (18–20) and adults (25–28) while they perform an intentional binding task. In this task, participants pressed a button (action) that delivered a tone (outcome) after a small delay and reported the time of the tone using the Libet clock. This action-outcome condition alternated with a no-action condition where an identical tone was triggered by a computer. Mid-adolescents showed greater outcome binding, such that they perceived self-triggered tones as being temporally closer to their actions compared to adults. Suggesting greater agency experience over the outcomes of their voluntary actions during mid-adolescence. Consistent with this, greater levels of attenuated neural response to self-triggered auditory tones (specifically P2 attenuation) were found during mid-adolescence compared to older age groups. This enhanced attenuation decreased with age as observed in outcome binding. However, there were no age-related differences in the readiness potential leading to the voluntary action (button press) as well as in the N1 attenuation to the self-triggered tones. Notably, in mid-adolescents greater outcome binding scores were positively associated with greater P2 attenuation, and smaller negativity in the late readiness potential. These findings suggest that the greater experience of implicit agency observed during mid-adolescence may be mediated by a neural over-suppression of action outcomes (auditory P2 attenuation), and over-reliance on motor preparation (late readiness potential), which we found to become adult-like during late-adolescence. Implications for adolescent development and SoA related neurodevelopmental disorders are discussed. © 2021 Elsevier Ltd