文献类型：期刊文献

英文题名：Astrocytic Phenotypic Switching in Posterior Piriform Cortex Orchestrates Bone Cancer Pain-Depression Comorbidity via Purinergic-Noradrenergic Signaling

作者：Liu, Jiang-Ping[1,2,3];Zhang, Jun-Han[4];Tan, Zhi-Xuan[5];Yan, Wei-Bing[4];Yuan, Ya-Ru[4];Liu, Yao[4];Wei, Bing-Di[6];Ding, Meng-Qi[4];Fu, Zhuo-Min[1,2,3];Liu, Ying[3];Wang, An-Qi[1,2,3];Ma, Lin[1,2,3];Li, Yong-Hong[1,2,3];Chai, Er-Qing[7];Wei, Chao-Jun[1,2,4]

第一作者：Liu, Jiang-Ping

通信作者：Liu, JP[1];Li, YH[1];Wei, CJ[1];Liu, JP[2];Li, YH[2];Wei, CJ[2];Liu, JP[3];Li, YH[3];Wei, CJ[4];Chai, EQ[5]

机构：[1]Gansu Prov Hosp, Inst Clin Res & Translat Med, Biobank & Bioinformat Engn Res Ctr, NHC Key Lab Diag & Therapy Gastrointestinal Tumor, Lanzhou, Peoples R China;[2]Lanzhou Univ, Sch Clin Med 3, Lanzhou, Peoples R China;[3]Gansu Univ Chinese Med, Sch Clin Med 1, Lanzhou, Peoples R China;[4]Gansu Univ Chinese Med, Sch Publ Hlth, Lanzhou, Peoples R China;[5]Qiqihar Med Univ, Dept Psychiat, Qiqihar, Peoples R China;[6]Guangzhou Med Univ, KingMed Sch Lab Med, Guangzhou, Peoples R China;[7]Gansu Prov Hosp, Cerebrovasc Dis Ctr, Lanzhou, Peoples R China

第一机构：Gansu Prov Hosp, Inst Clin Res & Translat Med, Biobank & Bioinformat Engn Res Ctr, NHC Key Lab Diag & Therapy Gastrointestinal Tumor, Lanzhou, Peoples R China

通信机构：[1]corresponding author), Gansu Prov Hosp, Inst Clin Res & Translat Med, Biobank & Bioinformat Engn Res Ctr, NHC Key Lab Diag & Therapy Gastrointestinal Tumor, Lanzhou, Peoples R China;[2]corresponding author), Lanzhou Univ, Sch Clin Med 3, Lanzhou, Peoples R China;[3]corresponding author), Gansu Univ Chinese Med, Sch Clin Med 1, Lanzhou, Peoples R China;[4]corresponding author), Gansu Univ Chinese Med, Sch Publ Hlth, Lanzhou, Peoples R China;[5]corresponding author), Gansu Prov Hosp, Cerebrovasc Dis Ctr, Lanzhou, Peoples R China.|[10735e9d5e7087247e71b]甘肃中医药大学公共卫生学院;[10735]甘肃中医药大学;

年份：2026

外文期刊名：ADVANCED SCIENCE

收录：;EI(收录号：20262320867400);Scopus(收录号：2-s2.0-105041018897);WOS:【SCI-EXPANDED(收录号:WOS:001784834500001)】；

基金：This work was supported by grants from the National Natural Science Foundation of China (82360236 to J.L.), Gansu Provincial Natural Science Foundation (23JRRA1299 to J.L.), Youth Talent Project of Gansu Province (2025QNGR67 to J.L.), Science and Technology Plan Project of Lanzhou (2023-4-59 to J.L.), Research Project of Gansu Provincial Hospital (23GSSYA-5 to J.L.), the Major Project of Gansu Provincial Department of Science and Technology Joint Research Fund (25JRRA1195 to E.C.), Key R&D Program of Gansu Province Science and Technology Program (24YFFA031 to C.W.), and Excellent Graduate Student Cultivation Project of Gansu Provincial Hospital (22GSSYD-57 to Z.T.).

语种：英文

外文关键词：adenosine A2A receptor; astrocyte-neuron crosstalk; comorbid depression symptoms in bone cancer pain; norepinephrine transporter dysregulation; posterior piriform cortex

摘要：Bone cancer pain occurs in up to 70% of patients with skeletal metastases and is accompanied by depression, severely diminishing quality of life. Current pharmacological strategies provide only partial relief, and the neurobiological mechanisms linking nociceptive and affective processing remain poorly defined. Herein, in a mouse model of Lewis lung carcinoma, we identify a previously uncharacterized astrocyte-neuron signaling axis in the posterior piriform cortex that underlies bone cancer pain with comorbid depression. Through metabolomic, proteomic, and fiber photometry approaches, we show that astrocytic phenotypic transition from the neuroprotective A2 to the neurotoxic A1 state triggers metabolic reprogramming, downregulates ATP/adenosine/adenosine A2A receptor signaling, and upregulates the norepinephrine transporter, impairing noradrenergic transmission. Interventions targeting astrocyte phenotypes, including minocycline and Lcn2 knockdown, normalized the posterior piriform cortex neurochemistry and alleviated both nociceptive and affective symptoms. These findings define a mechanistic framework in which astrocytic dysfunction orchestrates pain and depression, and highlight astrocyte-directed strategies for treating cancer pain-depression comorbidity.