نوع مقاله : مقاله مروری
نویسندگان
1 هیات علمی دانشگاه قم
2 1- گروه علوم ورزشی، دانشکده ادبیات و علوم انسانی،دانشگاه قم، قم، ایران.
چکیده
کلیدواژهها
موضوعات
عنوان مقاله [English]
نویسندگان [English]
Type 2 diabetes is associated with hippocampal neurometabolic dysfunction, increased oxidative stress, and decreased cognitive function, leading to diabetic encephalopathy. This systematic review and bioinformatics integration study aimed to evaluate the effect of exercise intervention and Spirulina supplementation on neuroenergetics/mitochondrial indices, oxidative stress, Type 2 diabetes is associated with hippocampal neurometabolic dysfunction, increased oxidative stress, and decreased cognitive function, leading to diabetic encephalopathy. This systematic review and bioinformatics integration study aimed to evaluate the effect of exercise intervention and Spirulina supplementation on neuroenergetics/mitochondrial indices, oxidative stressand behavioral outcomes of the hippocampus in diabetic rodent models. First, hippocampal general transcriptomic data (GEO/ENA) were analyzed; then, a comprehensive search based on PRISMA-2020 was performed in PubMed, Scopus, Web of Science, and gray sources. Screening and data extraction were performed by two independent reviewers, study quality was assessed with SYRCLE, effect sizes were standardized with Hedges’ g, and merged with a random-effects model in Comprehensive Meta-Analysis; Heterogeneity (I²), publication bias (funnel plot/Egger) and subgroup/regression analyses were reported based on intervention type, duration, intensity and timing. In the bioinformatics section, hub genes (such as PGC-1α/PPARGC1A, SOD2, UCP2, SIRT1/3, TFAM, AMPK) were extracted with PPI from STRING and WGCNA co-expression in Cytoscape, integrated with GO/KEGG enrichment in Enrichr and miRNA-mRNA network from miRTarBase/TargetScan, and the overlap of pathways/nodes with meta-analysis effects was measured via hypergeometric test. The results showed that exercise has a moderate to strong effect on improving mitochondrial biogenesis, energy homeostasis, autophagy/mitophagy, antioxidant response and behavior (g=0.72; 95% CI: 0.45–0.99; I²=42%), while Spirulina shows a moderate but significant effect (g=0.58; 95% CI: 0.31–0.85; I²=35%). In combined studies (exercise×Spirulina) it produced greater and more consistent improvements in metabolic/behavioral indices. Multilayer integration highlights the mechanistic convergence on the NAD⁺/SIRT–PGC-1α axis. Exercise mainly stimulates AMPK→CREB→PGC-1α/NRF1/TFAM transcription and Spirulina reduces oxidative/inflammatory stress through the Nrf2/ARE–SOD2 pathway. At the posttranscriptional level, key miRNAs (miR-23a/23b/696→PGC-1α; miR-34a/132/181a→SIRT1; miR-195/421→SIRT3; miR-146a/222→SOD2; miR-30e/miR-133a→UCP2; miR-590→TFAM; miR-451→CAB39/LKB1→AMPK indirect) explain the synergistic map. Each intervention alone is beneficial, but their combination is more likely to be synergistic and is more effective with circadian alignment (BMAL1/CLOCK). Limitations include the focus on animal models, heterogeneity in frequency/intensity/duration/timing, and lack of hippocampal-specific validation of miRNA interactions. Finally, the proposed precise therapeutic framework with 2×2 factorial RCT (HIIT/control × Spirulina/placebo), morning/evening scheduling, quality control of supplementation, and multimodal endpoints (cognition, hippocampal fMRI, BDNF, miRNA panel, and hub proteins) could facilitate cost-effective and biocompatible clinical translation to reduce the neurometabolic burden of diabetes.
Keywords: Hippocampus/ Spirulina/ Bioinformatics/ Gene Networks/ Exercise Activity/ Diabetic Encephalopathy
کلیدواژهها [English]
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