Altered expression and localization of synaptophysin in developing cerebellar cortex of neonatal rats due to maternal diabetes mellitus
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Published on: November 20, 2015
Javad Hami1, Saeed Vafaei-Nezhad2, Ghasem Ivar1
1Department of Anatomical Sciences, School of Medicine, Birjand University of Medical Sciences, Ghaffari St, Birjand, Iran.
Insights
Maternal diabetes during pregnancy impairs offspring cerebellar development by reducing synaptophysin expression, a key marker for synapse formation. Strict blood glucose control in mothers can normalize these negative effects on neurodevelopment.
Area of Science:
- Neuroscience
- Developmental Biology
- Endocrinology
Background:
- Pregnancy diabetes is linked to offspring neurodevelopmental issues.
- Synaptophysin (SYP) is crucial for synaptogenesis and synaptic density.
- Understanding maternal diabetes impact on cerebellar development is vital.
Purpose of the Study:
- To investigate the effects of maternal diabetes on synaptophysin (SYP) expression and localization in the developing rat cerebellum.
- To assess the impact on synaptogenesis and synaptic density in offspring exposed to maternal diabetes.
- To evaluate the potential of insulin treatment to mitigate these effects.
Main Methods:
- Wistar rats were made diabetic before and during pregnancy.
- Offspring were analyzed at postnatal days 0, 7, and 14.
- SYP mRNA expression and protein localization were assessed in cerebellar tissues.
Main Results:
- Maternal diabetes significantly downregulated SYP mRNA expression in offspring at P7 and P14.
- Reduced SYP localization was observed in specific cerebellar layers (EGL, ML) at P7.
- SYP expression decreased across cerebellar cortical layers at P14 in offspring of diabetic mothers.
- Insulin treatment in diabetic mothers prevented significant changes in SYP expression or localization.
Conclusions:
- Maternal diabetes adversely affects cerebellar synaptogenesis in offspring.
- Reduced synaptophysin expression is a key indicator of this developmental impairment.
- Effective maternal blood glucose control can normalize the negative impacts of diabetes on offspring neurodevelopment.
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.
