Effects of voluntary exercise and insulin glargine on learning and memory, oxidative stress indices, and synaptic proteins of young male offspring born to gestational diabetic dams

Abstract

Gestational diabetes mellitus (GDM) is associated with many complications at different stages of offspring’s lives, including neurological abnormalities and defects in learning and memory. The present study aimed to investigate the effect of voluntary exercise and insulin glargine administration in GDM rats on learning and memory, oxidative stress indices and expression of synaptic proteins in the hippocampus of young male offspring. Methods: In this study, 50 female Wistar rats (age 3 weeks) were used. The animals were divided into two groups: control (10 rats) and GDM (40 rats). The GDM model was induced using a high-fat/sucrose diet (HFD) for 6 weeks before mating and until the end of pregnancy. Animals in the control group received a standard diet during this period. Six weeks after receiving standard diet or HFD, rats were mated for pregnancy. Blood sugar above 140 mg/dl on the 7th day of pregnancy was considered as successful induction of GDM. The rats fed with a standard diet in case of pregnancy were placed in the control group, and the rats in which GDM was successfully induced were divided into 4 groups including: GDM, GDM + voluntary exercise (running wheel), GDM + insulin glargine (5-7 units until the end of pregnancy) and GDM + voluntary exercise + insulin. The male offspring were separated from their mothers at postnatal day (PND) 21 and fed with standard food until PND40. Finally, the memory of young male offspring was evaluated using the New Object Recognition Test (NORT) and the Y-maze test. Also, the level of expression of BDNF, PSD95 and synaptophysin proteins using western blotting method and the level of oxidative stress indicators including lipid peroxidation (1), total antioxidant capacity (2) and activity of superoxide dismutase (SOD) and glutathione peroxidase enzymes. GPx) were measured in the hippocampus of offspring. Results: Voluntary exercise and insulin glargine, alone (p<0.05) or in combination (p<0.01), in mothers with GDM could improve memory disorders caused by GDM and compensate for the decrease in BDNF (p<0.01 for the treatment and p < 0.001 for combined treatment) caused by GDM in the hippocampus of offspring. Voluntary exercise alone failed to prevent GDM-induced decreases in PSD-95 (p<0.05) and synaptophysin expression, and insulin glargine alone only increased PSD-95 expression. However, the combination treatment (p<0.001) was able to increase the expression of both factors. Also, exercise alone (p<0.01) or combined with insulin glargine (p<0.001) could improve all oxidative stress indicators, but insulin glargine alone could only reduce lipid peroxidation (p<0.01) and increase TAC (p<0.05), but had no significant effect on SOD and GPx enzymes activity.