TY - JOUR TI - Stimulation of hypothalamic oxytocin neurons suppresses colorectal cancer progression in mice AU - Pan, Susu AU - Yin, Kaili AU - Tang, Zhiwei AU - Wang, Shuren AU - Chen, Zhuo AU - Wang, Yirong AU - Zhu, Hongxia AU - Han, Yunyun AU - Liu, Mei AU - Jiang, Man AU - Xu, Ningzhi AU - Zhang, Guo A2 - Blevins, Ernie A2 - Zaidi, Mone A2 - Roizen, Jeff VL - 10 PY - 2021 DA - 2021/09/16 SP - e67535 C1 - eLife 2021;10:e67535 DO - 10.7554/eLife.67535 UR - https://doi.org/10.7554/eLife.67535 AB - Emerging evidence suggests that the nervous system is involved in tumor development in the periphery, however, the role of the 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, for example, celastrol, might be a novel strategy for colorectal cancer treatment. KW - hypothalamus KW - oxytocin neuron KW - colorectal cancer KW - tumor progression JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -