title: 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.
authors.affiliation: Department of Biosciences, São Paulo Federal University (UNIFESP), Santos, São Paulo, Brazil.
authors.forename: João Carlos
authors.initials: JC
authors.lastname: Diegues
authors.forename: José Rodrigo
authors.initials: JR
authors.lastname: Pauli
authors.forename: Eliete
authors.initials: E
authors.lastname: Luciano
authors.forename: José Alexandre Curiacos
authors.initials: JA
authors.lastname: de Almeida Leme
authors.forename: Leandro Pereira
authors.initials: LP
authors.lastname: de Moura
authors.forename: Rodrigo Augusto
authors.initials: RA
authors.lastname: Dalia
authors.forename: Michel Barbosa
authors.initials: MB
authors.lastname: de Araújo
authors.forename: Clarice Yoshiko
authors.initials: CY
authors.lastname: Sibuya
authors.forename: Maria Alice Rostom
authors.initials: MA
authors.lastname: de Mello
authors.forename: Ricardo José
authors.initials: RJ
authors.lastname: Gomes
mesh_terms: D000818:Animals; D001774:Blood Chemical Analysis; D001786:Blood Glucose; D015153:Blotting, Western; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D006624:Hippocampus / Q000503:physiopathology; D006943:Hyperglycemia / Q000503:physiopathology; D007328:Insulin / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D009043:Motor Activity; D010805:Physical Conditioning, Animal; D011897:Random Allocation; D017208:Rats, Wistar; D065852:Spatial Memory / Q000502:physiology*; D013550:Swimming; D013647:Task Performance and Analysis
chemical_list: D001786:Blood Glucose; D007328:Insulin; C548904:insulin-like growth factor-1, rat; D007334:Insulin-Like Growth Factor I
keywords: IGF-1; diabetes; exercise; hippocampus; water maze