Background and Purpose
Diabetes mellitus is a metabolic disorder affecting vital organs including the liver, kidneys, and heart, leading to diminished quality of life and increased mortality, particularly in aging populations. Beyond its systemic complications, diabetes is increasingly recognized as a brain-specific disorder wherein neuronal apoptosis contributes to pathological alterations. Impaired glucose metabolism and energy deficits commonly co-occur with cognitive, learning, and memory impairments in diabetic patients—so much so that Alzheimer’s disease is proposed as “type 3 diabetes.” Lifestyle modifications, such as appropriate diet and exercise, have been shown to improve and manage this progressively debilitating condition.This study aimed to investigate the effects of a 4-week aerobic exercise regimen combined with Spirulina supplementation on fasting blood glucose and gene expression within the BDNF/p75 neurotrophin signaling pathway in the hippocampus of streptozotocin-induced diabetic rats.
Materials and Methods
Twenty-eight male Wistar rats (8 weeks old, 230–260 g) were rendered diabetic via single intraperitoneal injection of streptozotocin (50 mg/kg). Seventy-two hours post-injection, fasting blood glucose was measured from the tail vein; diabetes was confirmed for glucose levels exceeding 200 mg/dL. Rats were randomized into four groups: diabetes control, diabetes with Spirulina supplementation, diabetes with aerobic exercise, and diabetes with both exercise and Spirulina.Spirulina groups received daily gavage of 500 mg/kg body weight Spirulina, five days per week for four weeks. Exercise groups underwent treadmill training with zero incline and progressive speed increases from 12 to 22 cm/s over sessions lasting 20 to 45 minutes, preceded and concluded by 15 minutes of warming up and cooling down at 10 cm/s. The combined group received Spirulina gavage 30 minutes prior to exercise. Control group rats were exposed to a quiet treadmill environment without exercise.Fasting glucose was assessed pre-injection, and at two- and four-week intervals post-injection. Seventy-two hours following the last training session, rats were anesthetized (ketamine 60 mg/kg and xylazine 8 mg/kg, intraperitoneal), and hippocampal tissues were harvested under rapid decapitation, then stored at −80°C until analysis. BDNF and p75 gene expressions were quantified via RT-PCR. Data were statistically analyzed using one-way ANOVA with Tukey post hoc testing at P ≤ 0.05.
Results
Two weeks after diabetes induction, all groups exhibited significant elevation in fasting blood glucose compared to baseline, without between-group variation. At four weeks, aerobic exercise, Spirulina supplementation, and their combination significantly reduced fasting glucose relative to diabetic controls, although levels did not return to baseline.Hippocampal analysis revealed significantly reduced BDNF expression in diabetic controls. The combined exercise plus Spirulina group showed notably higher BDNF expression than other groups (F = 22.5; p ≤ 0.001). No significant difference existed between exercise-only and Spirulina-only groups (p=0.3).Conversely, the diabetic group had markedly elevated p75NTR expression compared to other groups (F = 27.2; p ≤ 0.001). The combined intervention significantly lowered p75 expression, with no difference between exercise-only and Spirulina-only groups (p = 0.3). Detailed gene expression levels with standard errors are presented in the accompanying table.
Conclusion
Aerobic exercise and Spirulina supplementation, singularly or combined, significantly reduced fasting glucose and modulated BDNF and p75NTR gene expression in streptozotocin diabetic rats. The combined intervention elicited superior effects, potentially reflecting enhanced glucose uptake mediated by endurance training and antioxidative, anti-apoptotic properties of Spirulina. Both interventions stimulate neurotrophin activity, upregulating BDNF and downregulating its apoptotic receptor p75NTR, promoting neuronal preservation and mitigating diabetes-associated cognitive decline.
Article Message
This study underscores the importance of lifestyle factors in diabetes management. While individually effective, combining exercise and dietary supplementation yields the most pronounced benefits in glycemic control and neuroprotective molecular changes, highlighting the necessity of integrated therapeutic approaches.
Ethical Considerations
All experimental protocols adhered to national guidelines for laboratory animal care and were approved by the University of Isfahan Ethics Committee (Code: IR.UI.REC.1403.037).
Authors’ Contributions
Conceptualization: Sayed Mohammad Marandi, Maryam Ahmadi Rad
Data Collection: Fatemeh Jafarian
Data Analysis: Zeinab Rezaee
Manuscript Writing: Fatemeh Jafarian
Review and Editing: Zeinab Rezaee
Literature Review: Fatemeh Jafarian
Project Manager: Zeinab Rezaee
Conflict of Interest
The authors declare no conflicts of interest.
Acknowledgments
The authors gratefully acknowledge all contributors who assisted throughout this study.