Central Nervous System Transcriptomic Profiling of Ulcerative Colitis Mice Treated with Electroacupuncture at Tianshu (ST25) or Zusanli (ST36)
Jie Zhang, Xihui Zheng, Chenyang Wang, Xixi Liu, Zhu Zhao, Yi Sun, Guang Zuo, Yanfen SheBackground
Electroacupuncture (EA) can effectively relieve intestinal inflammatory injury in ulcerative colitis (UC). Tianshu (ST25) and Zusanli (ST36) are core acupoints for intestinal disorders, yet their central nervous system (CNS) mechanisms underlying UC amelioration remain unclear.
Methods
Dextran sulfate sodium-induced UC mice received EA at ST25 or ST36. Disease Activity Index (DAI) scores, colon length and colonic pathology were assessed. Hippocampus, brainstem and hypothalamus were collected for transcriptomic sequencing, bioinformatics analysis and immunofluorescence staining.
Results
Both EA groups improved DAI, colon shortening and colonic injury, and activated neurons in the brainstem and hypothalamus. In the brainstem: Differentially expressed genes (DEGs) from the ST25 EA group were enriched in biological complexes related to lipoprotein particles and lipid metabolism, alongside the PPAR signaling pathway; DEGs from the ST36 EA group were clustered in immune-inflammatory processes such as leukocyte activation and cytokine signaling, together with the Ras and MAPK signaling pathways. In the hypothalamus: DEGs of the ST25 EA group were overrepresented in pathways linked to Cushing syndrome; DEGs of the ST36 EA group were enriched in terms of leukocyte intercellular adhesion and myeloid leukocyte activation, together with the PPAR, Ras and MAPK signaling pathways.
Conclusions
EA at ST25 or ST36 alleviated symptoms and colonic pathological injury in UC mice, accompanied by increased brainstem and hypothalamic c-Fos expression, suggesting a potential correlation between activation of these brain regions and intervention effects. Transcriptomic analyses revealed that ST25 electroacupuncture was associated with the PPAR signaling pathway, lipid metabolism and energy homeostasis, while ST36 electroacupuncture correlated with the Ras/MAPK pathway and immune-inflammatory and oxidative-stress networks.