Early pheromone perception remodels neurodevelopment and accelerates neurodegeneration in adult C. elegans
Jing-Yi Peng,
Xuqing Liu,
Xian-Ting Zeng,
Yue Hao,
Jia-Hui Zhang,
Qian Li,
Xia-Jing Tong
Affiliations
Jing-Yi Peng
School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; Institute of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China
Xuqing Liu
School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China
Xian-Ting Zeng
School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China
Yue Hao
School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; Institute of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China
Jia-Hui Zhang
School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; Institute of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China; Lingang Laboratory, Shanghai 200031, China
Qian Li
Songjiang Institute and Songjiang Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201600, China; Center for Brain Science, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China; Department of Anatomy and Physiology, Ministry of Education-Shanghai Key Laboratory of Children’s Environmental Health in Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Xia-Jing Tong
School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; Corresponding author
Summary: Age-associated neurodegenerative disorders such as Parkinson’s and Alzheimer’s diseases are mainly caused by protein aggregation. The etiologies of these neurodegenerative diseases share a chemical environment. However, how chemical cues modulate neurodegeneration remains unclear. Here, we found that in Caenorhabditis elegans, exposure to pheromones in the L1 stage accelerates neurodegeneration in adults. Perception of pheromones ascr#3 and ascr#10 is mediated by chemosensory neurons ASK and ASI. ascr#3 perceived by G protein-coupled receptor (GPCR) DAF-38 in ASK activates glutamatergic transmission into AIA interneurons. ascr#10 perceived by GPCR STR-2 in ASI activates the secretion of neuropeptide NLP-1, which binds to the NPR-11 receptor in AIA. Activation of both ASI and ASK is required and sufficient to remodel neurodevelopment via AIA, which triggers insulin-like signaling and inhibits autophagy in adult neurons non-cell-autonomously. Our work reveals how pheromone perception at the early developmental stage modulates neurodegeneration in adults and provides insights into how the external environment impacts neurodegenerative diseases.
