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Insulin-Like Growth Factor-1 Receptor Is Differentially Distributed in Developing Cerebellar Cortex of Rats Born to
Javad Hami1, Saeed Vafaei-Nezhad1, Delaram Haghir2
1Department of Anatomical Sciences, School of Medicine, Birjand University of Medical Sciences, Birjand, Iran.
Insights
Maternal diabetes alters insulin-like growth factor-1 receptor (IGF-1R) distribution in developing rat cerebellum. This impacts granular and Purkinje cell development, highlighting risks for offspring neurodevelopment.
Area of Science:
- Neuroscience
- Developmental Biology
- Endocrinology
Background:
- Insulin-like growth factor-1 (IGF-1) is crucial for central nervous system (CNS) development.
- Maternal diabetes increases offspring risk for neurodevelopmental abnormalities, including motor and learning deficits.
Purpose of the Study:
- To investigate the impact of maternal diabetes on IGF-1 receptor (IGF-1R) distribution in the developing rat cerebellum.
- To assess changes in cerebellar volume and IGF-1R+ cell populations in offspring of diabetic mothers.
Main Methods:
- Wistar rats were made diabetic before and during pregnancy.
- Offspring were analyzed at postnatal days P0, P7, and P14.
- Cerebellar volume and IGF-1R+ cell densities in specific layers (IGL, ML) were quantified.
Main Results:
- Offspring of diabetic mothers showed increased cerebellar volume (except at P0) and higher IGF-1R+ granular cell densities in IGL and ML at P0.
- A reduction in IGF-1R+ granular and Purkinje cells was observed in the IGL of neonates from diabetic mothers at P7 and P14.
- Insulin treatment normalized cerebellar volume and IGF-1R+ cell counts compared to controls.
Conclusions:
- Maternal diabetes significantly alters IGF-1R localization within the developing cerebellar cortex.
- These changes in IGF-1R distribution may underlie the observed neurodevelopmental deficits in offspring.
- Insulin therapy can mitigate the adverse effects of maternal diabetes on cerebellar development.
Abstract:
Insulin-like growth factor-1 (IGF-1) has an important role in development of the central nervous system (CNS). Maternal diabetes is associated with a higher risk of developmental abnormalities in their offspring including motor dysfunction and learning deficits. The present study aimed to investigate the effects of maternal diabetes on the distribution pattern of IGF-1 receptor (IGF-1R) in the developing rat cerebellar cortex. Wistar female rats were maintained diabetic from a week before pregnancy through parturition, and male offspring was killed at P0, P7, and P14. In spite of P0, there was a significant increase in the total cerebellar volume in the pups born to diabetic mothers. In diabetic group, the IGF-1R+ granular cell densities in internal granular (IGL) and molecular (ML) layers were increased at P0. Moreover, the number of positive granular and Purkinje cells in the IGL of diabetic neonates' cerebellum was reduced in comparison with the control group at P7 and P14. There were no differences either in volume or in the number of IGF-1R+ cells in the layers of the cerebellar cortex between the insulin-treated diabetic group and controls. Our data indicate that diabetes in pregnancy strikingly influence the localization of IGF-1R in the developing cerebellar cortex.
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