Exercise Promotes Hippocampal Neurogenesis in T2DM Mice via Irisin/TLR4/MyD88/NF-κB-Mediated Neuroinflammation Pathway
Neuroinflammation is a major feature of type 2 diabetic mellitus (T2DM), adversely affecting hippocampal neurogenesis. However, the precise mechanism is not fully understood, and therapeutic approaches are currently lacking. Therefore, we determined the effects of exercise on neuroinflammation and h...
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2024-10-01
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| author | Haocheng Xu Xin Tian Yuanxin Wang Junjie Lin Baishu Zhu Chen Zhao Bin Wang Xin Zhang Yu Sun Nan Li Xun Sun Fanxi Zeng Mingzhi Li Xiquan Ya Renqing Zhao |
| author_facet | Haocheng Xu Xin Tian Yuanxin Wang Junjie Lin Baishu Zhu Chen Zhao Bin Wang Xin Zhang Yu Sun Nan Li Xun Sun Fanxi Zeng Mingzhi Li Xiquan Ya Renqing Zhao |
| author_sort | Haocheng Xu |
| collection | DOAJ |
| description | Neuroinflammation is a major feature of type 2 diabetic mellitus (T2DM), adversely affecting hippocampal neurogenesis. However, the precise mechanism is not fully understood, and therapeutic approaches are currently lacking. Therefore, we determined the effects of exercise on neuroinflammation and hippocampal neurogenesis in T2DM mice, with a specific focus on understanding the role of the irisin and related cascade pathways in modulating the beneficial effects of exercise in these processes. Ten-week exercise significantly decreased T2DM-induced inflammation levels and markedly promoted hippocampal neurogenesis and memory function. However, these positive effects were reversed by 10 weeks of treatment with cyclo RGDyk, an inhibitor of irisin receptor signaling. Additionally, exercise helped reduce the M1 phenotype polarization of hippocampal microglia in diabetic mice; this effect could be reversed with cyclo RGDyk treatment. Moreover, exercise markedly increased the levels of fibronectin type III domain-containing protein 5 (FNDC5)/irisin protein while decreasing the expression of Toll-like receptor 4 (TLR4), myeloid differential protein-88 (MyD88), and nuclear factor kappa-B (NF-κB) in the hippocampus of T2DM mice. However, blocking irisin receptor signaling counteracted the down-regulation of TLR4/MyD88/NF-κB in diabetic mice undergoing exercise intervention. Conclusively, exercise appears to be effective in reducing neuroinflammation and enhancing hippocampal neurogenesis and memory in diabetes mice. The positive effects are involved in the participation of the irisin/TLR4/MyD88/NF-κB signaling pathway, highlighting the potential of exercise in the management of diabetic-induced cognitive decline. |
| format | Article |
| id | doaj-art-7e76c277dc8547ac8b71fa42237ee853 |
| institution | OA Journals |
| issn | 2079-7737 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | MDPI AG |
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| series | Biology |
| spelling | doaj-art-7e76c277dc8547ac8b71fa42237ee8532025-08-20T02:10:57ZengMDPI AGBiology2079-77372024-10-01131080910.3390/biology13100809Exercise Promotes Hippocampal Neurogenesis in T2DM Mice via Irisin/TLR4/MyD88/NF-κB-Mediated Neuroinflammation PathwayHaocheng Xu0Xin Tian1Yuanxin Wang2Junjie Lin3Baishu Zhu4Chen Zhao5Bin Wang6Xin Zhang7Yu Sun8Nan Li9Xun Sun10Fanxi Zeng11Mingzhi Li12Xiquan Ya13Renqing Zhao14College of Physical Education, Yangzhou University, Yangzhou 225127, ChinaCollege of Physical Education, Yangzhou University, Yangzhou 225127, ChinaCollege of Physical Education, Yangzhou University, Yangzhou 225127, ChinaCollege of Physical Education, Yangzhou University, Yangzhou 225127, ChinaCollege of Physical Education, Yangzhou University, Yangzhou 225127, ChinaCollege of Physical Education, Yangzhou University, Yangzhou 225127, ChinaCollege of Physical Education, Yangzhou University, Yangzhou 225127, ChinaCollege of Physical Education, Yangzhou University, Yangzhou 225127, ChinaCollege of Physical Education, Yangzhou University, Yangzhou 225127, ChinaCollege of Physical Education, Yangzhou University, Yangzhou 225127, ChinaCollege of Physical Education, Yangzhou University, Yangzhou 225127, ChinaCollege of Physical Education, Yangzhou University, Yangzhou 225127, ChinaCollege of Physical Education, Yangzhou University, Yangzhou 225127, ChinaCollege of Physical Education, Yangzhou University, Yangzhou 225127, ChinaCollege of Physical Education, Yangzhou University, Yangzhou 225127, ChinaNeuroinflammation is a major feature of type 2 diabetic mellitus (T2DM), adversely affecting hippocampal neurogenesis. However, the precise mechanism is not fully understood, and therapeutic approaches are currently lacking. Therefore, we determined the effects of exercise on neuroinflammation and hippocampal neurogenesis in T2DM mice, with a specific focus on understanding the role of the irisin and related cascade pathways in modulating the beneficial effects of exercise in these processes. Ten-week exercise significantly decreased T2DM-induced inflammation levels and markedly promoted hippocampal neurogenesis and memory function. However, these positive effects were reversed by 10 weeks of treatment with cyclo RGDyk, an inhibitor of irisin receptor signaling. Additionally, exercise helped reduce the M1 phenotype polarization of hippocampal microglia in diabetic mice; this effect could be reversed with cyclo RGDyk treatment. Moreover, exercise markedly increased the levels of fibronectin type III domain-containing protein 5 (FNDC5)/irisin protein while decreasing the expression of Toll-like receptor 4 (TLR4), myeloid differential protein-88 (MyD88), and nuclear factor kappa-B (NF-κB) in the hippocampus of T2DM mice. However, blocking irisin receptor signaling counteracted the down-regulation of TLR4/MyD88/NF-κB in diabetic mice undergoing exercise intervention. Conclusively, exercise appears to be effective in reducing neuroinflammation and enhancing hippocampal neurogenesis and memory in diabetes mice. The positive effects are involved in the participation of the irisin/TLR4/MyD88/NF-κB signaling pathway, highlighting the potential of exercise in the management of diabetic-induced cognitive decline.https://www.mdpi.com/2079-7737/13/10/809diabetescognitionadult hippocampal neurogenesisexerciseneuroinflammation |
| spellingShingle | Haocheng Xu Xin Tian Yuanxin Wang Junjie Lin Baishu Zhu Chen Zhao Bin Wang Xin Zhang Yu Sun Nan Li Xun Sun Fanxi Zeng Mingzhi Li Xiquan Ya Renqing Zhao Exercise Promotes Hippocampal Neurogenesis in T2DM Mice via Irisin/TLR4/MyD88/NF-κB-Mediated Neuroinflammation Pathway Biology diabetes cognition adult hippocampal neurogenesis exercise neuroinflammation |
| title | Exercise Promotes Hippocampal Neurogenesis in T2DM Mice via Irisin/TLR4/MyD88/NF-κB-Mediated Neuroinflammation Pathway |
| title_full | Exercise Promotes Hippocampal Neurogenesis in T2DM Mice via Irisin/TLR4/MyD88/NF-κB-Mediated Neuroinflammation Pathway |
| title_fullStr | Exercise Promotes Hippocampal Neurogenesis in T2DM Mice via Irisin/TLR4/MyD88/NF-κB-Mediated Neuroinflammation Pathway |
| title_full_unstemmed | Exercise Promotes Hippocampal Neurogenesis in T2DM Mice via Irisin/TLR4/MyD88/NF-κB-Mediated Neuroinflammation Pathway |
| title_short | Exercise Promotes Hippocampal Neurogenesis in T2DM Mice via Irisin/TLR4/MyD88/NF-κB-Mediated Neuroinflammation Pathway |
| title_sort | exercise promotes hippocampal neurogenesis in t2dm mice via irisin tlr4 myd88 nf κb mediated neuroinflammation pathway |
| topic | diabetes cognition adult hippocampal neurogenesis exercise neuroinflammation |
| url | https://www.mdpi.com/2079-7737/13/10/809 |
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