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    Effects of prenatal binge-like ethanol exposure and maternal stress on postnatal morphological development of hippocampal neurons in rats
    (Pergamon-Elsevier Science Ltd, 2017) Jakubowska-Dogru, Ewa; Elibol, Birsen; Dursun, İlknur; Yürüker, Sinan
    Background: Alcohol is one of the most commonly used drugs of abuse negatively affecting human health and it is known as a potent teratogen responsible for fetal alcohol syndrome (FAS), which is characterized by cognitive deficits especially pronounced in juveniles but ameliorating in adults. Searching for the potential morphological correlates of these effects, in this study, we compared the course of developmental changes in the morphology of principal hippocampal neurons in fetal-alcohol (A group), intubated control (IC group), and intact control male rats (C group) over a protracted period of the first two postnatal months. Methods: Ethanol was administered to the pregnant Wistar dams intragastrically, throughout gestation days (GD) 7-20, at a total dose of 6 g/kg/day resulting in the mean blood alcohol concentration (BAC) of 246.6 +/- 40.9 mg/dl. Ten morphometric parameters of Golgi-stained hippocampal neurons (pyramidal and granule) from CA1, CA3, and DG areas were examined at critical postnatal days (PD): at birth (PD1), at the end of the brain growth spurt period (PD10), in juveniles (PD30), and in young adults (PD60). Results: During postnatal development, the temporal pattern of morphometric changes was shown to be region dependent with most significant alterations observed between PD1-30 in the CA region and between PD10-30 in the DG region. It was also parameter-dependent with the soma size (except for CA3 pyramids), number of primary dendrites, dendrite diameter, dendritic tortuosity and the branch angle demonstrating little changes, while the total dendritic field area, dendritic length, number of dendritic bifurcations, and spine density being highly increased in all hippocampal regions during the first postnatal month. Moderate ethanol intoxication and the maternal intubation stress during gestation, showed similar, transient effects on the neuron development manifested as a smaller soma size in granule cells, reduced dendritic parameters and lower spine density in pyramidal neurons at PD1. Full recovery from these effects took place within the first 10 postnatal days. Conclusions: This study showed regional and temporal differences in the development of different morphometric features of principal hippocampal neurons in intact subjects over a protracted 2-months postnatal period. It also demonstrated an overlap in the effects of a moderate fetal ethanol intoxication and a mild maternal stress produced by the intragastric intubation, a commonly used method of ethanol administration to the pregnant dams. Fast recovery from the adverse effects on the soma size, dendritic arborization and spines density observed at birth indicates towards the fetal ethanol/stress induced developmental retardation.
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    Öğe
    The structural effects of Vitamin A deficiency on biological macromolecules due to ethanol consumption and withdrawal: An FTIR study with chemometrics
    (2022) Elibol, Birsen; Severcan, Mete; Jakubowska-Dogru, Ewa; Dursun, Ilknur; Severcan, Feride
    The structural effects of vitamin A-deficiency were examined on the molecular profiles of biomolecules of male rat hippocampus during prolonged ethanol intake/withdrawal using FT-IR spectroscopy coupled with chemometrics. Liquid ethanol diet with/without vitamin A was maintained to adult rats for 3-months. The rats were decapitated at different ethanol withdrawal times and FT-IR spectra were obtained. Ethanol consumption/withdrawal produced significant changes in proteins' conformations, while having insignificant structural effects on lipids. In vitamin A deficiency, ethanol produced structural changes in lipids by lipid ordering especially in the early-ethanol withdrawal. Furthermore, an increase in lipid and protein content, saturated/unsaturated lipid ratio, a decrease in nucleic acids content and decrease in membrane fluidity were observed. These changes were less severe in the presence of Vitamin A. This study is clinically important for individuals with vitamin A deficiency because they have to be more cautious when consuming alcohol to protect themselves from cognitive dysfunctions.