Postnatal treadmill exercise alleviates cognitive deficits in offspring exposed to gestational diabetes mellitus via reactivation of the hippocampal Wnt/β-catenin signaling pathway
Gestational diabetes mellitus (GDM) exposes the developing fetal brain to hyperglycemia and has been linked to adverse neurocognitive out-comes in offspring; however, effective postnatal strategies and underly-ing mechanisms remain incompletely defined. Here, we tested whether early-life aerobic exercise rescues hippocampus-dependent memory impairment and canonical Wnt/β-catenin signaling deficits in offspring born to dams with streptozotocin-induced GDM. Pregnant C57BL/6 mice received streptozotocin (40 mg/kg, gestational day 7) or saline. Male offspring were weaned and assigned to sedentary control or treadmill exercise (15 m/min, 60 min/day, 5 days/wk, 2 weeks), generat-ing four groups: saline control (Sal-CON, n=12), saline exercise (Sal-Ex, n=12), GDM control (GDM-CON, n=12), and GDM exercise (GDM-Ex, n=12). Spatial learning and reference memory were assessed using the Morris water maze, and spatial working memory was evaluated with a T-maze task. Hippocampal expression of Wnt3, β-catenin, and glycogen synthase kinase-3β (GSK-3β) was quantified by Western blot-ting. GDM offspring exhibited impaired hippocampal memory perfor-mance, evidenced by a reduced hidden-to-visible platform latency ratio in the Morris water maze and loss of novelty preference in the T-maze. These behavioral deficits were accompanied by suppression of canon-ical Wnt signaling, with decreased hippocampal Wnt3 and β-catenin and increased GSK-3β in GDM-CON compared with controls. Notably, postnatal treadmill exercise significantly improved both reference and working memory and normalized Wnt/β-catenin pathway components in GDM offspring. Collectively, these findings indicate that early-life aer-obic exercise mitigates GDM-associated cognitive vulnerability, at least in part, by reactivating hippocampal Wnt/β-catenin signaling.
목차
Abstract INTRODUCTION MATERIALS AND METHODS Experimental animals GDM induction and grouping Treadmill exercise protocol Morris water maze T-maze test Western blotting Statistical analysis RESULTS Treadmill exercise alleviates spatial learning and reference memory deficits in GDM offspring Treadmill exercise improves spatial working memory performance in GDM offspring Treadmill exercise modulates the hippocampal Wnt/β-catenin signaling pathway in GDM offspring DISCUSSION CONFLICT OF INTEREST ACKNOWLEDGMENTS REFERENCES
Kyung-Wan Baek [ Department of Physical Education, Gyeongsang National University/Research Institute of Pharmaceutical Sciences, Gyeongsang National University, Jinju, Korea ]
Jong-Hwa Won [ Department of Physical Education, Gyeongsang National University, Jinju, Korea ]
Sam-Jun Lee [ Department of Sport Rehabilitation, College of Health, Welfare and Education, Tongmyong University, Busan, Korea ]
Corresponding Author