Diabetes during pregnancy enhanced neuronal death in the hippocampus of rat offspring

• Significant differences in the total number of neuronal cells in the vaious hippocampal subfields in the rat offspring born to diabetic animals.
• A striking difference in the density of TUNEL positive cells in the different subregions of hippocampus in pups born to diabetic mothers.
• A probable mechanism for the effects of maternal diabetes on neurobehavioral and neurocognitive deficits in the offspring is proposed.
• The mechanism relies on the apoptosis induction in the cells of developing hippocampus due to diabetes in pregnancy.

BackgroundDiabetes in pregnancy has a detrimental effect on central nervous system (CNS) development and is associated with an increased risk of short- and long-term neurocognitive impairment in the offspring. This study aimed to investigate the effect of maternal diabetes and also insulin treatment on the numerical density of apoptotic cells in rat neonate’s hippocampi during the first two postnatal weeks.MethodsWistar female rats were maintained diabetic from a week before gestation through parturition and their male pup’s brains were collected at postnatal days (P); P0, P7 and P14, equivalent to the third trimester in human. Numerical density of total neurons and percentage of apoptotic (TUNEL-positive) cells in different subfields of hippocampus (CA1, CA2, CA3, and DG) was calculated by stereological methods.ResultsImmediately after birth, we found a significantly decline in the total neuronal density only in hippocampal CA3 area in neonates born to diabetic animals (p < 0.0001). Moreover, the number of neurons was significantly decreased in all hippocampal sub-regions of diabetic group pups when compared to control and insulin treated diabetic pups at both P7 and P14 (p < 0.0001 each). Nevertheless, in diabetic group, the percentage of apoptotic cells in different subfields of hippocampus were higher in all studied time-points compared to control or insulin treated diabetic groups (p < 0.0001 each). There were no significant differences either in the total number or apoptotic cells in the different hippocampal sub-fields between the insulin-treated diabetic group and controls (p > 0.05).ConclusionOur data indicate that diabetes in pregnancy induce the neuronal cell apoptosis in offspring hippocampus. Furthermore, the maternal glycaemia control by insulin treatment in the most cases normalized these effects.