Abstract
Diabetes can be classified as type 1, type 2, and gestational diabetes mellitus (GDM). It has been reported that children born from mothers with GDM present motor impairment, however, underlying mechanisms of GDM-induce fetal neurological diseases remain unknown. In this study, NOD (nonobese diabetic) mice were used to construct the GDM model; after 2 weeks of gestation, thalamocortical axon development of fetal was evaluated by immunofluorescence. PCR of LRRC4C was used to confirm axon development of the thalamus cortex. RNA array was used to predict possible targets affected by GDM during fetal neurodevelopment. Western blot was used to investigate the underlying mechanism, PI3K inhibitor, and MAPK inhibitor was used to determine key pathway involved in this model, in vitro axonal growth was evaluated using neural stem cells, tactile sensory behavior of offspring was assessed to confirm neurological influence further. The result shown that maternal diabetes significantly suppressed axonal development of fetal thalamus cortex, PCR array of GDM fetal brain indicated that upregulation of GLP-1R compared with normal fetal, ELISA confirmed that GLP-1 level was decreased in GDM maternal serum compared with that of wild type pregnant mice. In vitro study observed enhanced axonal elongation after supplements of GLP-1 analog, GLP-1 analog PI3K-dependently active ROCK1 activity, IP injection of GLP-1 analog could partly reverse GDM-induced suppression of fetal thalamocortical axon development and improve tactile sensory behavior of GDM offspring. Our study provided a novel mechanism of GDM induced-neurological diseases and predicted GLP-1 as possible prevention supplement during gestation.