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Diabetes in Pregnancy Adversely Affects the Expression of Glycogen Synthase Kinase-3β in the Hippocampus of Rat Neonates

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Abstract

Diabetes during pregnancy causes a wide range of neurodevelopmental and neurocognitive abnormalities in offspring. Glycogen synthase kinase-3 (GSK-3) is widely expressed during brain development and regulates multiple cellular processes, and its dysregulation is implicated in the pathogenesis of diverse neurodegenerative and psychological diseases. This study was designed to examine the effects of maternal diabetes on GSK-3β messenger RNA (mRNA) expression and phosphorylation in the developing rat hippocampus. Female rats were maintained diabetic from a week before pregnancy through parturition, and male offspring was killed immediately after birth. We found a significant bilateral upregulation of GSK-3β mRNA expression in the hippocampus of pups born to diabetic mothers at P0, compared to controls. Moreover, at the same time point, there was a marked bilateral increase in the phosphorylation level of GSK-3β in the diabetic group. Unlike phosphorylation levels, there was a significant upregulation in hippocampal GSK-3β mRNA expression in the insulin-treated group, when compared to controls. The present study revealed that diabetes during pregnancy strongly influences the regulation of GSK-3β in the right/left developing hippocampi. These dysregulations may be part of the cascade of events through which diabetes during pregnancy affects the newborn’s hippocampal structure and function.

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Acknowledgments

This paper is based on the results of Razieh Karimi M.Sc. thesis (No. A-529) which financially was supported by a Mashhad University of Medical Sciences (MUMS) grant.

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The authors declare that they have no competing interests.

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Authors and Affiliations

  1. Department of Anatomical Sciences, Faculty of Medicine, Birjand University of Medical Sciences, Birjand, Iran

    Javad Hami

  2. Medical Genetics Research Center (MGRC), School of Medicine, Mashhad University of Medical Sciences (MUMS), Mashhad, Iran

    Razieh Karimi, Hossein Haghir & Ariane Sadr-Nabavi

  3. Department of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences (MUMS), Azadi Square, Mashhad, Iran

    Razieh Karimi & Ariane Sadr-Nabavi

  4. Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences (MUMS), Mashhad, Iran

    Hossein Haghir

  5. Division of Human Genetics, Immunology Research Center, Avicenna Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran

    Mehran Gholamin

  6. Molecular Medicine Research Department, Iranian Academic Centers for Education, Culture and Research (ACECR)-Khorasan Razavi Branch, Mashhad, Iran

    Ariane Sadr-Nabavi

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  1. Javad Hami
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  2. Razieh Karimi
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Correspondence to Ariane Sadr-Nabavi.

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Javad Hami and Razieh Karimi contributed equally to this work.

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Hami, J., Karimi, R., Haghir, H. et al. Diabetes in Pregnancy Adversely Affects the Expression of Glycogen Synthase Kinase-3β in the Hippocampus of Rat Neonates. J Mol Neurosci 57, 273–281 (2015). https://doi.org/10.1007/s12031-015-0617-3

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