Advanced Science (Nov 2024)
Lysosomal TFEB‐TRPML1 Axis in Astrocytes Modulates Depressive‐like Behaviors
- Jia‐Wen Mo,
- Peng‐Li Kong,
- Li Ding,
- Jun Fan,
- Jing Ren,
- Cheng‐Lin Lu,
- Fang Guo,
- Liang‐Yu Chen,
- Ran Mo,
- Qiu‐Ling Zhong,
- You‐Lu Wen,
- Ting‐Ting Gu,
- Qian‐Wen Wang,
- Shu‐Ji Li,
- Ting Guo,
- Tian‐Ming Gao,
- Xiong Cao
Affiliations
- Jia‐Wen Mo
- Key Laboratory of Mental Health of the Ministry of Education Guangdong‐Hong Kong‐Macao Greater Bay Area Center for Brain Science and Brain‐Inspired Intelligence Guangdong‐Hong Kong Joint Laboratory for Psychiatric Disorders Guangdong Province Key Laboratory of Psychiatric Disorders Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases Department of Neurobiology School of Basic Medical Sciences Southern Medical University Guangzhou 510515 China
- Peng‐Li Kong
- Key Laboratory of Mental Health of the Ministry of Education Guangdong‐Hong Kong‐Macao Greater Bay Area Center for Brain Science and Brain‐Inspired Intelligence Guangdong‐Hong Kong Joint Laboratory for Psychiatric Disorders Guangdong Province Key Laboratory of Psychiatric Disorders Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases Department of Neurobiology School of Basic Medical Sciences Southern Medical University Guangzhou 510515 China
- Li Ding
- Key Laboratory of Mental Health of the Ministry of Education Guangdong‐Hong Kong‐Macao Greater Bay Area Center for Brain Science and Brain‐Inspired Intelligence Guangdong‐Hong Kong Joint Laboratory for Psychiatric Disorders Guangdong Province Key Laboratory of Psychiatric Disorders Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases Department of Neurobiology School of Basic Medical Sciences Southern Medical University Guangzhou 510515 China
- Jun Fan
- Key Laboratory of Mental Health of the Ministry of Education Guangdong‐Hong Kong‐Macao Greater Bay Area Center for Brain Science and Brain‐Inspired Intelligence Guangdong‐Hong Kong Joint Laboratory for Psychiatric Disorders Guangdong Province Key Laboratory of Psychiatric Disorders Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases Department of Neurobiology School of Basic Medical Sciences Southern Medical University Guangzhou 510515 China
- Jing Ren
- Key Laboratory of Mental Health of the Ministry of Education Guangdong‐Hong Kong‐Macao Greater Bay Area Center for Brain Science and Brain‐Inspired Intelligence Guangdong‐Hong Kong Joint Laboratory for Psychiatric Disorders Guangdong Province Key Laboratory of Psychiatric Disorders Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases Department of Neurobiology School of Basic Medical Sciences Southern Medical University Guangzhou 510515 China
- Cheng‐Lin Lu
- Key Laboratory of Mental Health of the Ministry of Education Guangdong‐Hong Kong‐Macao Greater Bay Area Center for Brain Science and Brain‐Inspired Intelligence Guangdong‐Hong Kong Joint Laboratory for Psychiatric Disorders Guangdong Province Key Laboratory of Psychiatric Disorders Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases Department of Neurobiology School of Basic Medical Sciences Southern Medical University Guangzhou 510515 China
- Fang Guo
- Key Laboratory of Mental Health of the Ministry of Education Guangdong‐Hong Kong‐Macao Greater Bay Area Center for Brain Science and Brain‐Inspired Intelligence Guangdong‐Hong Kong Joint Laboratory for Psychiatric Disorders Guangdong Province Key Laboratory of Psychiatric Disorders Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases Department of Neurobiology School of Basic Medical Sciences Southern Medical University Guangzhou 510515 China
- Liang‐Yu Chen
- Key Laboratory of Mental Health of the Ministry of Education Guangdong‐Hong Kong‐Macao Greater Bay Area Center for Brain Science and Brain‐Inspired Intelligence Guangdong‐Hong Kong Joint Laboratory for Psychiatric Disorders Guangdong Province Key Laboratory of Psychiatric Disorders Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases Department of Neurobiology School of Basic Medical Sciences Southern Medical University Guangzhou 510515 China
- Ran Mo
- Key Laboratory of Mental Health of the Ministry of Education Guangdong‐Hong Kong‐Macao Greater Bay Area Center for Brain Science and Brain‐Inspired Intelligence Guangdong‐Hong Kong Joint Laboratory for Psychiatric Disorders Guangdong Province Key Laboratory of Psychiatric Disorders Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases Department of Neurobiology School of Basic Medical Sciences Southern Medical University Guangzhou 510515 China
- Qiu‐Ling Zhong
- Key Laboratory of Mental Health of the Ministry of Education Guangdong‐Hong Kong‐Macao Greater Bay Area Center for Brain Science and Brain‐Inspired Intelligence Guangdong‐Hong Kong Joint Laboratory for Psychiatric Disorders Guangdong Province Key Laboratory of Psychiatric Disorders Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases Department of Neurobiology School of Basic Medical Sciences Southern Medical University Guangzhou 510515 China
- You‐Lu Wen
- Department of Psychology and Behavior Guangdong 999 Brain Hospital Institute for Brain Research and Rehabilitation South China Normal University Guangzhou 510515 China
- Ting‐Ting Gu
- Department of Psychology and Behavior Guangdong 999 Brain Hospital Institute for Brain Research and Rehabilitation South China Normal University Guangzhou 510515 China
- Qian‐Wen Wang
- Department of Bioinformatics School of Basic Medical Sciences Southern Medical University Guangzhou 510515 China
- Shu‐Ji Li
- Key Laboratory of Mental Health of the Ministry of Education Guangdong‐Hong Kong‐Macao Greater Bay Area Center for Brain Science and Brain‐Inspired Intelligence Guangdong‐Hong Kong Joint Laboratory for Psychiatric Disorders Guangdong Province Key Laboratory of Psychiatric Disorders Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases Department of Neurobiology School of Basic Medical Sciences Southern Medical University Guangzhou 510515 China
- Ting Guo
- Key Laboratory of Mental Health of the Ministry of Education Guangdong‐Hong Kong‐Macao Greater Bay Area Center for Brain Science and Brain‐Inspired Intelligence Guangdong‐Hong Kong Joint Laboratory for Psychiatric Disorders Guangdong Province Key Laboratory of Psychiatric Disorders Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases Department of Neurobiology School of Basic Medical Sciences Southern Medical University Guangzhou 510515 China
- Tian‐Ming Gao
- Key Laboratory of Mental Health of the Ministry of Education Guangdong‐Hong Kong‐Macao Greater Bay Area Center for Brain Science and Brain‐Inspired Intelligence Guangdong‐Hong Kong Joint Laboratory for Psychiatric Disorders Guangdong Province Key Laboratory of Psychiatric Disorders Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases Department of Neurobiology School of Basic Medical Sciences Southern Medical University Guangzhou 510515 China
- Xiong Cao
- Key Laboratory of Mental Health of the Ministry of Education Guangdong‐Hong Kong‐Macao Greater Bay Area Center for Brain Science and Brain‐Inspired Intelligence Guangdong‐Hong Kong Joint Laboratory for Psychiatric Disorders Guangdong Province Key Laboratory of Psychiatric Disorders Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases Department of Neurobiology School of Basic Medical Sciences Southern Medical University Guangzhou 510515 China
- DOI
- https://doi.org/10.1002/advs.202403389
- Journal volume & issue
-
Vol. 11,
no. 41
pp. n/a – n/a
Abstract
Abstract Lysosomes are important cellular structures for human health as centers for recycling, signaling, metabolism and stress adaptation. However, the potential role of lysosomes in stress‐related emotions has long been overlooked. Here, it is found that lysosomal morphology in astrocytes is altered in the medial prefrontal cortex (mPFC) of susceptible mice after chronic social defeat stress. A screen of lysosome‐related genes revealed that the expression of the mucolipin 1 gene (Mcoln1; protein: mucolipin TRP channel 1) is decreased in susceptible mice and depressed patients. Astrocyte‐specific knockout of mucolipin TRP channel 1 (TRPML1) induced depressive‐like behaviors by inhibiting lysosomal exocytosis‐mediated adenosine 5′‐triphosphate (ATP) release. Furthermore, this stress response of astrocytic lysosomes is mediated by the transcription factor EB (TFEB), and overexpression of TRPML1 rescued depressive‐like behaviors induced by astrocyte‐specific knockout of TFEB. Collectively, these findings reveal a lysosomal stress‐sensing signaling pathway contributing to the development of depression and identify the lysosome as a potential target organelle for antidepressants.
Keywords