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Prenatal alcohol–induced neuroapoptosis in rat brain cerebral cortex: protective effect of folic acid and betaine

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Abstract

Purpose

Alcohol consumption in pregnancy may cause fetal alcohol syndrome (FAS) in the infant. This study aims to investigate prenatal alcohol exposure related neuroapoptosis on the cerebral cortex tissues of newborn rats and possible neuroprotective effects of betaine, folic acid, and combined therapy.

Methods

Pregnant rats were divided into five experimental groups: control, ethanol, ethanol + betaine, ethanol + folic acid, and ethanol + betaine + folic acid combined therapy groups. We measured cytochrome c release, caspase-3, calpain and cathepsin B and L. enzyme activities. In order to observe apoptotic cells in the early stages, TUNEL method was chosen together with histologic methods such as assessing the diameters of the apoptotic cells, their distribution in unit volume and volume proportion of cortical intact neuron nuclei.

Results

Calpain, caspase-3 activities, and cytochrome c levels were significantly increased in alcohol group while cathepsin B and L. activities were also found to be elevated albeit not statistically significant. These increases were significantly reversed by folic acid and betaine + folic acid treatments. While ethanol increased the number of apoptotic cells, this increase was prevented in ethanol + betaine and ethanol + betaine + folic acid groups. Morphometric examination showed that the mean diameter of apoptotic cells was increased with ethanol administration while this increase was reduced by betaine and betaine + folic acid treatments.

Conclusion

We observed that ethanol is capable of triggering apoptotic cell death in the newborn rat brains. Furthermore, folic acid, betaine, and combined therapy of these supplements may reduce neuroapoptosis related to prenatal alcohol consumption, and might be effective on preventing fetal alcohol syndrome in infants.

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Acknowledgements

This work was supported by TUBITAK 109S510 project.

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Authors and Affiliations

  1. Vocational School of Health Services, Istanbul Bilim University, Yazarlar Sok. No:17, 34394, Istanbul, Turkey

    Ibrahim Sogut

  2. Vocational School of Health Services, Eskisehir Osmangazi University, 26480, Eskisehir, Turkey

    Onur Uysal

  3. Medical School, Department of Biochemistry, Eskisehir Osmangazi University, 26480, Eskisehir, Turkey

    Aysegul Oglakci, Kazim Kartkaya & Gungor Kanbak

  4. Medical School, Department of Anatomy, Eskisehir Osmangazi University, 26480, Eskisehir, Turkey

    Ferruh Yucel

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  1. Ibrahim Sogut
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  2. Onur Uysal
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Correspondence to Ibrahim Sogut.

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Sogut, I., Uysal, O., Oglakci, A. et al. Prenatal alcohol–induced neuroapoptosis in rat brain cerebral cortex: protective effect of folic acid and betaine. Childs Nerv Syst 33, 407–417 (2017). https://doi.org/10.1007/s00381-016-3309-6

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  • DOI: https://doi.org/10.1007/s00381-016-3309-6

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