Journal
JOURNAL OF MOLECULAR NEUROSCIENCE
Volume 57, Issue 2, Pages 273-281Publisher
HUMANA PRESS INC
DOI: 10.1007/s12031-015-0617-3
Keywords
Maternal diabetes; Glycogen synthase kinase-3 beta; Hippocampus; Rat newborn
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Funding
- Mashhad University of Medical Sciences (MUMS) grant [A-529]
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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-3 beta 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-3 beta 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-3 beta in the diabetic group. Unlike phosphorylation levels, there was a significant upregulation in hippocampal GSK-3 beta 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-3 beta 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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