Sarm1-mediated neurodegeneration within the enteric nervous system protects against local inflammation of the colon.
10.1007/s13238-021-00835-w
- Author:
Yue SUN
1
;
Qi WANG
1
;
Yi WANG
1
;
Wenran REN
2
;
Ying CAO
1
;
Jiali LI
3
;
Xin ZHOU
4
;
Wei FU
4
;
Jing YANG
5
Author Information
1. State Key Laboratory of Membrane Biology, School of Life Sciences, Center for Life Sciences, Peking University, Beijing, 100871, China.
2. School of Medicine, Tsinghua University, Beijing, 100084, China.
3. IDG/McGovern Institute for Brain Research, Peking University, Beijing, 100871, China.
4. Department of General Surgery, Peking University Third Hospital, Beijing, 100191, China.
5. State Key Laboratory of Membrane Biology, School of Life Sciences, Center for Life Sciences, Peking University, Beijing, 100871, China. jing.yang@pku.edu.cn.
- Publication Type:Journal Article
- Keywords:
3D imaging;
Sarm1;
axonal degeneration;
catecholaminergic axons;
colitis;
enteric nervous system;
neurodegeneration
- From:
Protein & Cell
2021;12(8):621-638
- CountryChina
- Language:English
-
Abstract:
Axonal degeneration is one of the key features of neurodegenerative disorders. In the canonical view, axonal degeneration destructs neural connections and promotes detrimental disease defects. Here, we assessed the enteric nervous system (ENS) of the mouse, non-human primate, and human by advanced 3D imaging. We observed the profound neurodegeneration of catecholaminergic axons in human colons with ulcerative colitis, and similarly, in mouse colons during acute dextran sulfate sodium-induced colitis. However, we unexpectedly revealed that blockage of such axonal degeneration by the Sarm1 deletion in mice exacerbated the colitis condition. In contrast, pharmacologic ablation or chemogenetic inhibition of catecholaminergic axons suppressed the colon inflammation. We further showed that the catecholaminergic neurotransmitter norepinephrine exerted a pro-inflammatory function by enhancing the expression of IL-17 cytokines. Together, this study demonstrated that Sarm1-mediated neurodegeneration within the ENS mitigated local inflammation of the colon, uncovering a previously-unrecognized beneficial role of axonal degeneration in this disease context.
