Neurodegeneration of catecholaminergic axons involved the local energy deficit and depended on Sarm1. (A–C) The degeneration of catecholaminergic axons in the colon was caused by TNFα. (A) The wild-type mice were subjected to the DSS-induced colitis. TNFα mRNA levels in the colon tissues were determined by the qPCR analysis. n = 5, mean ± SEM, *P < 0.01 (ANOVA test). (B and C) The wild-type mice were administered with the anti-TNFα neutralizing antibody or control IgG and then subjected to the DSS-induced colitis. The unsectioned colon tissues were processed for the whole-tissue TH-immunolabeling. (B) Representative 3D-projection images (longitudinal view) of the 500-μm thickness of the tissues at 12.6× magnification of the lightsheet imaging. (C) TH-positive catecholaminergic axons within the mucosa were quantified. n = 5, mean ± SEM, *P < 0.01 (ANOVA test). (D–G) TNFα directly triggered the axonal degeneration of catecholaminergic neurons of the celiac ganglia. Catecholaminergic neurons of the celiac ganglia of wild-type mice were in vitro cultured. The neurons were then treated with 50 ng/mL recombinant TNFα, in combination with 10 mmol/L methylpyruvate or 50 mmol/L nicotinamide. (D) Representative images of TH-positive axons of the cultured catecholaminergic neurons. (E) The integrity of TH-positive catecholaminergic axons was quantified. n = 4, mean ± SEM, *P < 0.01 (ANOVA test). (F and G) ATP (F) or NAD+ (G) levels of the catecholaminergic neurons were measured. n = 4, mean ± SEM, *P < 0.01 (ANOVA test). (H to K) TNFα-triggered axonal degeneration of catecholaminergic neurons of the celiac ganglia depended on Sarm1. Catecholaminergic neurons of the celiac ganglia of Sarm1+/+ or Sarm1-/- mice were in vitro cultured and then treated with 50 ng/mL recombinant TNFα. (H) Representative images of TH-positive axons of the cultured catecholaminergic neurons. (I) The integrity of TH-positive catecholaminergic axons was quantified. n = 4, mean ± SEM, *P < 0.01 (ANOVA test). (J and K) ATP (J) or NAD+ (K) levels of the catecholaminergic neurons were measured. n = 4, mean ± SEM, *P < 0.01 (ANOVA test)
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