Emerging evidence suggests that the nervous system is involved in tumor development in the periphery, however, the role of central nervous system remains largely unknown. Here, by combining genetic, chemogenetic, pharmacological and electrophysiological approaches, we show that hypothalamic oxytocin (Oxt)-producing neurons modulate colitis-associated cancer (CAC) progression in mice. Depletion or activation of Oxt neurons could augment or suppress CAC progression. Importantly, brain treatment with celastrol, a pentacyclic triterpenoid, excites Oxt neurons and inhibits CAC progression, and this anti-tumor effect was significantly attenuated in Oxt neuron-lesioned mice. Furthermore, brain treatment with celastrol suppresses sympathetic neuronal activity in the celiac-superior mesenteric ganglion (CG-SMG), and activation of β2 adrenergic receptor abolishes the anti-tumor effect of Oxt neuron activation or centrally administered celastrol. Taken together, these findings demonstrate that hypothalamic Oxt neurons regulate CAC progression by modulating the neuronal activity in the CG-SMG. Stimulation of Oxt neurons using chemicals, eg. celastrol, might be a novel strategy for colorectal cancer treatment.
All data that support the findings of this study are included in this published article and its supplementary files. Source data files have been provided for Figures 1-7.
- Guo Zhang
- Guo Zhang
- Mei Liu
- Yunyun Han
- Man Jiang
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: Animal procedures were approved by the IACUC at Huazhong University of Science and Technology (#2511).
- Ernie Blevins
- Received: February 14, 2021
- Accepted: September 12, 2021
- Accepted Manuscript published: September 16, 2021 (version 1)
© 2021, Pan et al.
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