Memory impairment and depressive-like phenotype are accompanied by downregulation of hippocampal insulin and BDNF signaling pathways in prediabetic mice.

Prediabetes is the stage before diabetes in which not all the symptoms or signs required to diagnose diabetes are present, but blood glucose is abnormally high. This study investigates if memory impairment and depressive-like phenotype are accompanied by the hippocampal insulin and BDNF signaling in prediabetic mice. Male adult Swiss mice received streptozotocin (STZ, 200 mg/kg, ip) to induce prediabetes. Control mice were treated with citrate buffer (5 ml/kg, ip). To characterize prediabetes status, metabolic parameters were determined in mice. The behavioral test battery to assess memory consisted of object recognition (ORT), object location (OLT), and Morris water maze (MWM) tests. The mouse depressive-like phenotype was investigated using the forced swimming (FST) and tail suspension (TST) tests. The pIRS-1/Akt/GLUT4 and BDNF/TrkB/CREB protein contents were determined in the hippocampus of mice. Prediabetic mice showed mild hyperglycemia, reduced body weight gain, and an increase in glucose and insulin tolerance tests (AUCs). Prediabetic mice had smaller recognition and location indexes, in the ORT and OLT, than the control group. Prediabetic mice showed hippocampus-dependent spatial memory impairment, in the MWM test, and an increase in immobility time, in the TST and FST, compared to the control group. The molecular findings indicate the downregulation of hippocampal insulin and BDNF signaling in prediabetic mice. In conclusion, memory impairment and depressive-like phenotype were potentially linked to the downregulation of hippocampal pIRS-1/Akt/GLUT4 and BDNF/CREB signaling in prediabetic mice.