Stimulation of hypothalamic oxytocin neurons suppresses colorectal cancer progression in mice

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 oxy...

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Autores principales:	Susu Pan, Kaili Yin, Zhiwei Tang, Shuren Wang, Zhuo Chen, Yirong Wang, Hongxia Zhu, Yunyun Han, Mei Liu, Man Jiang, Ningzhi Xu, Guo Zhang
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	hypothalamus oxytocin neuron colorectal cancer tumor progression Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/a6da26d2c0804a2bbd58e67a215885f3
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spelling	oai:doaj.org-article:a6da26d2c0804a2bbd58e67a215885f32021-11-15T05:42:03ZStimulation of hypothalamic oxytocin neurons suppresses colorectal cancer progression in mice10.7554/eLife.675352050-084Xe67535https://doaj.org/article/a6da26d2c0804a2bbd58e67a215885f32021-09-01T00:00:00Zhttps://elifesciences.org/articles/67535https://doaj.org/toc/2050-084XEmerging 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.Susu PanKaili YinZhiwei TangShuren WangZhuo ChenYirong WangHongxia ZhuYunyun HanMei LiuMan JiangNingzhi XuGuo ZhangeLife Sciences Publications Ltdarticlehypothalamusoxytocin neuroncolorectal cancertumor progressionMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	hypothalamus oxytocin neuron colorectal cancer tumor progression Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	hypothalamus oxytocin neuron colorectal cancer tumor progression Medicine R Science Q Biology (General) QH301-705.5 Susu Pan Kaili Yin Zhiwei Tang Shuren Wang Zhuo Chen Yirong Wang Hongxia Zhu Yunyun Han Mei Liu Man Jiang Ningzhi Xu Guo Zhang Stimulation of hypothalamic oxytocin neurons suppresses colorectal cancer progression in mice
description	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.
format	article
author	Susu Pan Kaili Yin Zhiwei Tang Shuren Wang Zhuo Chen Yirong Wang Hongxia Zhu Yunyun Han Mei Liu Man Jiang Ningzhi Xu Guo Zhang
author_facet	Susu Pan Kaili Yin Zhiwei Tang Shuren Wang Zhuo Chen Yirong Wang Hongxia Zhu Yunyun Han Mei Liu Man Jiang Ningzhi Xu Guo Zhang
author_sort	Susu Pan
title	Stimulation of hypothalamic oxytocin neurons suppresses colorectal cancer progression in mice
title_short	Stimulation of hypothalamic oxytocin neurons suppresses colorectal cancer progression in mice
title_full	Stimulation of hypothalamic oxytocin neurons suppresses colorectal cancer progression in mice
title_fullStr	Stimulation of hypothalamic oxytocin neurons suppresses colorectal cancer progression in mice
title_full_unstemmed	Stimulation of hypothalamic oxytocin neurons suppresses colorectal cancer progression in mice
title_sort	stimulation of hypothalamic oxytocin neurons suppresses colorectal cancer progression in mice
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/a6da26d2c0804a2bbd58e67a215885f3
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_version_	1718428573371465728

Stimulation of hypothalamic oxytocin neurons suppresses colorectal cancer progression in mice

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