Spatial memory in sedentary and trained diabetic rats: Molecular mechanisms

Abstract

Diabetes mellitus is a chronic disease that has been associated with memory loss, neurological disorders, and Alzheimer's disease. Some studies show the importance of physical exercise to prevent and minimize various neurological disorders. It is believed that the positive effects of exercise on brain functions are mediated by brain insulin and insulin-like growth factor-1 (IGF-1) signaling. In this study, we investigate the role of swimming exercise training on hippocampus proteins related to insulin/IGF-1 signaling pathway in Type 1 diabetic rats and its effects on spatial memory. Wistar rats were divided into four groups namely sedentary control, trained control, sedentary diabetic (SD), and trained diabetic (TD). Diabetes was induced by Alloxan (ALX) (32 mg/kg b.w.). The training program consisted in swimming 5 days/week, 1 h/day, per 6 weeks, supporting an overload corresponding to 90% of the anaerobic threshold. We employed ALX-induced diabetic rats to explore learning and memory abilities using Morris water maze test. At the end of the training period, the rats were sacrificed 48 h after their last exercise bout when blood samples were collected for serum glucose, insulin, and IGF-1 determinations. Hippocampus was extracted to determinate protein expression (IR, IGF-1R, and APP) and phosphorylation (AKT-1, AKT-2, Tau, and β-amyloide proteins) by Western Blot analysis. All dependent variables were analyzed by two-way analysis of variance with significance level of 5%. Diabetes resulted in hyperglycemia and hypoinsulinemia in both SD and TD groups (P < 0.05); however, in the training-induced group, there was a reduction in blood glucose in TD. The average frequency in finding the platform decreased in SD rats; however, exercise training improved this parameter in TD rats. Aerobic exercise decreased Tau phosphorylation and APP expression, and increased some proteins related to insulin/IGF-1 pathway in hippocampus of diabetic rats. Thus, these molecular adaptations from exercise training might contribute to improved spatial learning and memory in diabetic organisms.

Effects of the swimming exercise on the consolidation and persistence of auditory and contextual fear memory

“…Inoue et al [23] reported rats that ran on the treadmill for 60 min/day, 5 times a week over 6 weeks exhibited higher spatial memory performance than sedentary rats when tested in the Morris Water Maze 24 hours after memory training. Swimming exercise has been related to the retention of short-term memory [24][25][26][27][28][29][30]. Diegues et al [24] demonstrated that rats submitted to swimming exercise over 6 weeks showed an improved spatial memory evaluated by the lower escape latency in the retention test when compared to rats of the control group.…”

“…Swimming exercise has been related to the retention of short-term memory [24][25][26][27][28][29][30]. Diegues et al [24] demonstrated that rats submitted to swimming exercise over 6 weeks showed an improved spatial memory evaluated by the lower escape latency in the retention test when compared to rats of the control group. In addition, rats submitted to swimming exercise over 8 weeks [25] also showed an improved contextual memory assessed 24 hours after passive avoidance training.…”

“…However, there are few reports in the literature regarding the role of physical exercise in implicit memory related to the paradigm of tone/foot shock conditioning [24,25], especially at the persistence phase. Moreover, there are no reports in the literature investigating the effects of swimming exercise on the experimental paradigm of implicit memory.…”

“…Moreover, there are no reports in the literature investigating the effects of swimming exercise on the experimental paradigm of implicit memory. Based on the current literature that reported positive effects of a protocol with six weeks of swimming exercise on the explicit memory [24], the present study aimed to investigate the relationship between swimming exercise and the consolidation and persistence of contextual and auditorycued fear memory.…”

Brain Alterations and Clinical Symptoms of Dementia in Diabetes: Aβ/Tau-Dependent and Independent Mechanisms

“…Taken together, these findings indicate that insulin/IGF signaling is impaired in the diabetic brain, and this signaling might have an impact on aging-related brain dysfunction (82). Interestingly, aerobic exercise increases some proteins related to the insulin/IGF-1 pathway in the hippocampus and improves spatial memory in diabetic rats (83). …”