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The impacts of diabetes in pregnancy on hippocampal synaptogenesis in rat neonates
S Vafaei-Nezhad1, J Hami1, A Sadeghi2
1Department of Anatomical Sciences, School of Medicine, Birjand University of Medical Sciences, Birjand, Iran.
Insights
Maternal diabetes negatively impacts offspring hippocampal development, reducing synaptogenesis markers like synaptophysin (SYP). Insulin treatment normalized these effects, highlighting the importance of glycemic control during pregnancy for neurodevelopment.
Area of Science:
- Neuroscience
- Developmental Biology
- Endocrinology
Background:
- Pregnancy diabetes negatively affects offspring neurodevelopment, leading to cognitive and behavioral issues.
- Synaptogenesis, crucial for memory, is impaired by maternal diabetes.
- Synaptophysin (SYP) is a key marker for synaptic vesicle development and function in the hippocampus.
Purpose of the Study:
- To investigate the impact of maternal diabetes on synaptophysin (SYP) expression and distribution in the developing rat hippocampus.
- To assess SYP as a marker of synaptogenesis affected by gestational diabetes.
- To evaluate the efficacy of insulin treatment in mitigating these effects.
Main Methods:
- Utilized Wistar rats, inducing diabetes in females before and during pregnancy.
- Analyzed offspring hippocampus at postnatal days 0, 7, and 14 using Immunofluorescence staining and real-time PCR.
- Quantified SYP mRNA expression and neuronal distribution patterns.
Main Results:
- Significant downregulation of SYP mRNA expression was observed in offspring from diabetic mothers at postnatal days 7 and 14.
- A marked decrease in SYP-positive hippocampal neurons was found in offspring of diabetic rats, particularly at 1 and 2 weeks of age.
- Insulin treatment prevented significant changes in SYP expression and distribution compared to controls.
Conclusions:
- Maternal diabetes adversely affects hippocampal synaptogenesis in offspring.
- SYP expression and distribution are reliable indicators of diabetes-induced neurodevelopmental deficits.
- Effective glycemic control with insulin during pregnancy can normalize these negative impacts on offspring brain development.
Abstract:
Diabetes during the pregnancy period impairs hippocampal development, and is associated with neurocognitive and neurobehavioral problems in the offspring. Synaptogenesis is one of the most important events in the development of the nervous system, and is known as a mechanism by which the memory process takes place. Synaptophysin (SYP) is an integral membrane protein of synaptic vesicles in the hippocampus involved also in learning and memory. The present study aimed to examine the effects of maternal diabetes on the expression and distribution pattern of SYP, as a marker of synaptogenesis, in the developing rat hippocampus using Immunofluorescence staining and real-time PCR. Wistar female rats were maintained as diabetic from a week before pregnancy through parturition and male offspring was euthanized at postnatal day (P) 0, 7, and 14. Our results showed a significant down-regulation in mRNA expression of SYP in the offspring born to diabetic animals at P7, and P14 (P ⩽ 0.05 each). Regarding to the density of SYP expressing hippocampal neurons, we found a marked decrease in the distribution pattern of SYP in all hippocampal subfields of Streptozotocin (STZ)-D group rat neonates, especially in one and two weeks of age (P ⩽ 0.05 each). Moreover, the results revealed no significant changes in either gene expression or distribution pattern of SYP--positive neurons in insulin-treated group compared with the controls. The present study demonstrated that diabetes in pregnancy has negative impacts on synaptogenesis in the offspring's hippocampus. Furthermore, the rigid maternal glycaemia control by insulin treatment in most cases normalized these effects.
