Aerobic exercise reverses the NF-κB/NLRP3 inflammasome/5-HT pathway by upregulating irisin to alleviate post-stroke depression.

Autor:	Tang XQ; Department of Rehabilitation Medicine, Department of Sports Medicine, Institute of Translational Medicine, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, China., Liao RY; The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine, Changsha, China., Zheng LJ; Department of Rehabilitation Medicine, Department of Sports Medicine, Institute of Translational Medicine, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, China., Yang LL; Department of Rehabilitation Medicine, Department of Sports Medicine, Institute of Translational Medicine, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, China., Ma ZL; Department of Rehabilitation Medicine, Department of Sports Medicine, Institute of Translational Medicine, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, China., Yi C; Department of Rehabilitation Medicine, Department of Sports Medicine, Institute of Translational Medicine, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, China., Liu J; Department of Rehabilitation Medicine, Department of Sports Medicine, Institute of Translational Medicine, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, China., Liu JC; College of Acupuncture-moxibustion, Tuina and Rehabilitation, Hunan University of Traditional Chinese Medicine, Changsha, China., Kuang YJ; College of Acupuncture-moxibustion, Tuina and Rehabilitation, Hunan University of Traditional Chinese Medicine, Changsha, China., Cai HA; Department of Rehabilitation Medicine, Department of Sports Medicine, Institute of Translational Medicine, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, China., Huang L; Department of Rehabilitation Medicine, Department of Sports Medicine, Institute of Translational Medicine, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, China.
Jazyk:	angličtina
Zdroj:	Annals of translational medicine [Ann Transl Med] 2022 Dec; Vol. 10 (24), pp. 1350.
DOI:	10.21037/atm-22-5443
Abstrakt:	Background: Post-stroke depression (PSD) is one of the most common and serious sequelae of stroke. The pathogenesis of PSD involves both psychosocial and biological mechanisms, and aerobic exercise is a potential therapeutic target. We conducted an in-depth exploration of the protective mechanisms of aerobic exercise in a PSD mouse model. Methods: In this study, C57BL/6 mice were used as the research objects, and a PSD mouse model was established by combining middle cerebral artery occlusion and chronic unpredictable mild stimulation. Real-time quantitative polymerase chain reaction, enzyme-linked immunosorbent assays, adeno-associated virus microinjection technology, co-immunoprecipitation, fluorescence in-situ hybridization, and western blotting were performed. A moderate-load treadmill exercise was used for aerobic exercise intervention. The moderate-intensity aerobic exercise training method adopted 0 slopes and treadmill adaptation training for 5 days. We verified the effects of aerobic exercise on the nuclear factor kappa B (NF-κB)/nucleotide-binding oligomerization domain--like receptor protein 3 (NLRP3) inflammasome/5-hydroxytryptamine (5-HT) pathway. Results: Aerobic exercise effectively alleviated the neurological damage caused by PSD (P<0.01). The results from the PSD mouse model in vivo were consistent with those of the cell experiments. Moreover, overexpression of irisin improves depression-like behavior in PSD mice. We confirmed that aerobic exercise is involved in PSD through 5-HT, which inhibits NF-κB/NLRP3 inflammasome initiation through irisin and alleviates mitochondrial damage under stress by reducing calcium overload, thereby inhibiting NLRP3 inflammasome activation. Conclusions: Aerobic exercise reversed the NF-κB/NLRP3 inflammasome/5-HT pathway by upregulating irisin expression to alleviate PSD. Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-5443/coif). The authors have no conflicts of interest to declare. (2022 Annals of Translational Medicine. All rights reserved.)
Databáze:	MEDLINE
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