Yu Shang1, Li Tian2, Tianjiao Chen1, Xiaoying Liu1, Jilin Zhang1, Dongxin Liu1, Jiayi Wei1, Wengang Fang1, Yuhua Chen3, Deshu Shang4. 1. Department of Developmental Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning Province, PR China. 2. Department of Geriatrics, Shengjing Hospital of China Medical University, No.36 Sanhao Street, Heping District, Shenyang, Liaoning Province, PR China. 3. Department of Developmental Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning Province, PR China. Electronic address: yhchen@cmu.edu.cn. 4. Department of Developmental Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning Province, PR China. Electronic address: dsshang@cmu.edu.cn.
Abstract
PURPOSE: Elevated levels of CXCL1 were observed in the cerebrospinal fluid of patients with early Alzheimer's disease, which may affect neural stem cells in the subventricular zone. We used APP/PS1 mice and neural stem cells to elucidate the role of CXCL1 in Alzheimer's disease. METHODS & RESULTS: We detected CXCL1 in cerebrospinal fluid (CSF), activated macrophages, and microglia suggesting that macrophages may contribute to elevated CXCL1 in the CSF of middle-aged APP/PS1 mice. Proliferation and differentiation of neural stem cells were further analyzed and the results suggested that CXCL1 promotes the proliferation of neural stem cells and inhibits their differentiation into astrocytes. In order to determine how CXCL1 exerts these effects, we analyzed intracellular reactive oxygen species, cell signaling, and performed in vivo recovery experiments. Our results suggest that CXCL1 promotes neural stem cell proliferation through a mechanism involving the production of reactive oxygen species and the PI3K/Akt pathway. CONCLUSION: In APP/PS1 mice, macrophage-derived CXCL1 can promote the proliferation of neural stem cells in the subventricular zone via the NOX2-ROS-PI3K/Akt pathway.
PURPOSE: Elevated levels of CXCL1 were observed in the cerebrospinal fluid of patients with early Alzheimer's disease, which may affect neural stem cells in the subventricular zone. We used APP/PS1mice and neural stem cells to elucidate the role of CXCL1 in Alzheimer's disease. METHODS & RESULTS: We detected CXCL1 in cerebrospinal fluid (CSF), activated macrophages, and microglia suggesting that macrophages may contribute to elevated CXCL1 in the CSF of middle-aged APP/PS1mice. Proliferation and differentiation of neural stem cells were further analyzed and the results suggested that CXCL1 promotes the proliferation of neural stem cells and inhibits their differentiation into astrocytes. In order to determine how CXCL1 exerts these effects, we analyzed intracellular reactive oxygen species, cell signaling, and performed in vivo recovery experiments. Our results suggest that CXCL1 promotes neural stem cell proliferation through a mechanism involving the production of reactive oxygen species and the PI3K/Akt pathway. CONCLUSION: In APP/PS1mice, macrophage-derived CXCL1 can promote the proliferation of neural stem cells in the subventricular zone via the NOX2-ROS-PI3K/Akt pathway.
Authors: Jan Korbecki; Magdalena Gąssowska-Dobrowolska; Jerzy Wójcik; Iwona Szatkowska; Katarzyna Barczak; Mikołaj Chlubek; Irena Baranowska-Bosiacka Journal: Int J Mol Sci Date: 2022-04-11 Impact factor: 6.208
Authors: Minji Jeon; Zhuorui Xie; John E Evangelista; Megan L Wojciechowicz; Daniel J B Clarke; Avi Ma'ayan Journal: BMC Bioinformatics Date: 2022-09-13 Impact factor: 3.307