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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.

No abstract

Anxiety disorder is characterized by excessive fear, anxiety, and avoidance of perceived threats in internal to oneself or the environment, however, the underlying mechanisms are less well understood. Here, we show that transforming growth factor‐β‐activated kinase 1 (Tak1) expressed in the astrocytes of mediobasal hypothalamus (MBH) plays a crucial role in anxiety‐like behavior in mice. Our data demonstrate that deficiency of Tak1 in astrocytes increased anxiety level, but did not impact locomotor activity in mice. Astrocytic activation of Tak1 in the MBH mitigated the anxiety‐like behavior, whereas suppression of Tak1 in MBH astrocytes promoted the anxiety‐like behavior in mice. Collectively, these data suggest that Tak1 expressed in the MBH astrocytes could modulate the anxiety‐like behavior in mice.