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Altered expression and localization of synaptophysin in developing cerebellar cortex of neonatal rats due to maternal diabetes mellitus

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Abstract

There is sufficient evidence that diabetes during pregnancy is associated with a higher risk of neurodevelopmental anomalies including learning deficits, behavioral problems and motor dysfunctions in the offspring. Synaptophysin (SYP) is an integral membrane protein of synaptic vesicles and is considered as a marker for synaptogenesis and synaptic density. This study aimed to examine the effects of maternal diabetes in pregnancy on the expression and localization of SYP in the developing rat cerebellum. Wistar female rats were maintained diabetic from a week before pregnancy through parturition and male offspring was euthanized at postnatal day (P) 0, 7, and 14. The results revealed a significant down-regulation in the mRNA expression of SYP in the offspring born to diabetic animals at both P7 and P14 (P < 0.05 each). One week after birth, there was a significant reduction in the localization of SYP expression in the external granular (EGL) and in the molecular (ML) layers of neonates born to diabetic animals (P < 0.05 each). We also found a marked decrease in the expression of SYP in all of the cerebellar cortical layers of STZ-D group pups at P14 (P < 0.05 each). Moreover, our results revealed no significant changes in either expression or localization of SYP in insulin-treated group pups when compared with the controls (P ≥ 0.05 each). The present study demonstrated that maternal diabetes has adverse effects on the synaptogenesis in the offspring’s cerebellum. Furthermore, the rigid maternal blood glucose control in the most cases normalized these negative impacts.

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Acknowledgments

This study was financially supported by Birjand University of Medical Sciences (BUMS) Grant (No. 1027). The authors gratefully thank to Prof. Ebrahim Esfandiari, Prof. Mohammad Mardani, Prof. Mohammad Afshar, Dr. Mohammad Mahdi Hasanzadeh Taheri, Prof. Shahnaz Razavi, Dr. Mohammad Fereidooni, and Mrs. Nassim Lotfi for their technical assistance and helpful comments.

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Authors and Affiliations

  1. Department of Anatomical Sciences, School of Medicine, Birjand University of Medical Sciences, Ghaffari St, Birjand, Iran

    Javad Hami, Saeed Vafaei-Nezhad & Ghasem Ivar

  2. Department of Anatomy and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

    Akram Sadeghi

  3. Department of Neurosurgery, School of Medicine, Birjand University of Medical Sciences, Birjand, Iran

    Kazem Ghaemi

  4. Central Lab, Isfahan University of Medical Sciences, Isfahan, Iran

    Mostafa Mostafavizadeh

  5. Department of Public Health, Deputy of Research and Technology, Research Centre of Experimental Medicine, Birjand University of Medical Sciences, Birjand, Iran

    Mehran Hosseini

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  1. Javad Hami
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Correspondence to Saeed Vafaei-Nezhad.

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Hami, J., Vafaei-Nezhad, S., Ivar, G. et al. Altered expression and localization of synaptophysin in developing cerebellar cortex of neonatal rats due to maternal diabetes mellitus. Metab Brain Dis 31, 1369–1380 (2016). https://doi.org/10.1007/s11011-016-9864-4

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  • DOI: https://doi.org/10.1007/s11011-016-9864-4

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