| Literature DB >> 35545672 |
Pengxiang Chen1,2,3,4, Wei Wang1,2,3, Rui Liu1,2,3, Jiahui Lyu5, Lei Zhang1,2,3,4, Baizhou Li6, Biying Qiu1,2,3,4, Anhao Tian1,2,3, Wenhong Jiang1,2,3,4, Honggang Ying1,2,3, Rui Jing1,2,3,4, Qianqian Wang7, Keqing Zhu4, Ruiliang Bai8, Linghui Zeng9, Shumin Duan1,2,3,5,10,11, Chong Liu12,13,14,15,16.
Abstract
Animals constantly receive various sensory stimuli, such as odours, sounds, light and touch, from the surrounding environment. These sensory inputs are essential for animals to search for food and avoid predators, but they also affect their physiological status, and may cause diseases such as cancer. Malignant gliomas-the most lethal form of brain tumour1-are known to intimately communicate with neurons at the cellular level2,3. However, it remains unclear whether external sensory stimuli can directly affect the development of malignant glioma under normal living conditions. Here we show that olfaction can directly regulate gliomagenesis. In an autochthonous mouse model that recapitulates adult gliomagenesis4-6 originating in oligodendrocyte precursor cells (OPCs), gliomas preferentially emerge in the olfactory bulb-the first relay of brain olfactory circuitry. Manipulating the activity of olfactory receptor neurons (ORNs) affects the development of glioma. Mechanistically, olfaction excites mitral and tufted (M/T) cells, which receive sensory information from ORNs and release insulin-like growth factor 1 (IGF1) in an activity-dependent manner. Specific knockout of Igf1 in M/T cells suppresses gliomagenesis. In addition, knocking out the IGF1 receptor in pre-cancerous mutant OPCs abolishes the ORN-activity-dependent mitogenic effects. Our findings establish a link between sensory experience and gliomagenesis through their corresponding sensory neuronal circuits.Entities:
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Year: 2022 PMID： 35545672 DOI： 10.1038/s41586-022-04719-9
Source DB: PubMed Journal: Nature ISSN： 0028-0836 Impact factor: 69.504