Modulation of glymphatic system by visual circuit activation alleviates memory impairment and apathy in a mouse model of Alzheimer’s disease
Abstract Alzheimer’s disease is characterized by progressive amyloid deposition and cognitive decline, yet the pathological mechanisms and treatments remain elusive. Here we report the therapeutic potential of low-intensity 40 hertz blue light exposure in a 5xFAD mouse model of Alzheimer’s disease....
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| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55678-w |
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| author | Wen Wu Yubai Zhao Xin Cheng Xiaoru Xie Yixiu Zeng Quan Tao Yishuai Yang Chuan Xiao Zhan Zhang Jiahui Pang Jian Jin Hongbo He Yangyang Lin Boxing Li Junxian Ma Xiaojing Ye Wei-Jye Lin |
| author_facet | Wen Wu Yubai Zhao Xin Cheng Xiaoru Xie Yixiu Zeng Quan Tao Yishuai Yang Chuan Xiao Zhan Zhang Jiahui Pang Jian Jin Hongbo He Yangyang Lin Boxing Li Junxian Ma Xiaojing Ye Wei-Jye Lin |
| author_sort | Wen Wu |
| collection | DOAJ |
| description | Abstract Alzheimer’s disease is characterized by progressive amyloid deposition and cognitive decline, yet the pathological mechanisms and treatments remain elusive. Here we report the therapeutic potential of low-intensity 40 hertz blue light exposure in a 5xFAD mouse model of Alzheimer’s disease. Our findings reveal that light treatment prevents memory decline in 4-month-old 5xFAD mice and motivation loss in 14-month-old 5xFAD mice, accompanied by restoration of glial water channel aquaporin-4 polarity, improved brain drainage efficiency, and a reduction in hippocampal lipid accumulation. We further demonstrate the beneficial effects of 40 hertz blue light are mediated through the activation of the vLGN/IGL-Re visual circuit. Notably, concomitant use of anti-Aβ antibody with 40 hertz blue light demonstrates improved soluble Aβ clearance and cognitive performance in 5xFAD mice. These findings offer functional evidence on the therapeutic effects of 40 hertz blue light in Aβ-related pathologies and suggest its potential as a supplementary strategy to augment the efficacy of antibody-based therapy. |
| format | Article |
| id | doaj-art-453ab7fcdec94a908416b0e6f35992ba |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-453ab7fcdec94a908416b0e6f35992ba2025-01-05T12:38:23ZengNature PortfolioNature Communications2041-17232025-01-0116112010.1038/s41467-024-55678-wModulation of glymphatic system by visual circuit activation alleviates memory impairment and apathy in a mouse model of Alzheimer’s diseaseWen Wu0Yubai Zhao1Xin Cheng2Xiaoru Xie3Yixiu Zeng4Quan Tao5Yishuai Yang6Chuan Xiao7Zhan Zhang8Jiahui Pang9Jian Jin10Hongbo He11Yangyang Lin12Boxing Li13Junxian Ma14Xiaojing Ye15Wei-Jye Lin16Department of Rehabilitation Medicine, Zhujiang Hospital, Southern Medical UniversityDepartment of Rehabilitation Medicine, Zhujiang Hospital, Southern Medical UniversityFaculty of Forensic Medicine, Zhongshan School of Medicine, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen UniversityFaculty of Forensic Medicine, Zhongshan School of Medicine, Sun Yat-sen UniversityDepartment of Rehabilitation Medicine, Zhujiang Hospital, Southern Medical UniversityGuangdong Provincial Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen UniversityDepartment of Rehabilitation Medicine, Zhujiang Hospital, Southern Medical UniversityDepartment of Rehabilitation Medicine, Zhujiang Hospital, Southern Medical UniversityGuangdong Mental Health Center, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical UniversityDepartment of Rehabilitation Medicine, the Sixth Affiliated Hospital, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen UniversityTianfu Xinglong Lake LaboratoryFaculty of Forensic Medicine, Zhongshan School of Medicine, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen UniversityAbstract Alzheimer’s disease is characterized by progressive amyloid deposition and cognitive decline, yet the pathological mechanisms and treatments remain elusive. Here we report the therapeutic potential of low-intensity 40 hertz blue light exposure in a 5xFAD mouse model of Alzheimer’s disease. Our findings reveal that light treatment prevents memory decline in 4-month-old 5xFAD mice and motivation loss in 14-month-old 5xFAD mice, accompanied by restoration of glial water channel aquaporin-4 polarity, improved brain drainage efficiency, and a reduction in hippocampal lipid accumulation. We further demonstrate the beneficial effects of 40 hertz blue light are mediated through the activation of the vLGN/IGL-Re visual circuit. Notably, concomitant use of anti-Aβ antibody with 40 hertz blue light demonstrates improved soluble Aβ clearance and cognitive performance in 5xFAD mice. These findings offer functional evidence on the therapeutic effects of 40 hertz blue light in Aβ-related pathologies and suggest its potential as a supplementary strategy to augment the efficacy of antibody-based therapy.https://doi.org/10.1038/s41467-024-55678-w |
| spellingShingle | Wen Wu Yubai Zhao Xin Cheng Xiaoru Xie Yixiu Zeng Quan Tao Yishuai Yang Chuan Xiao Zhan Zhang Jiahui Pang Jian Jin Hongbo He Yangyang Lin Boxing Li Junxian Ma Xiaojing Ye Wei-Jye Lin Modulation of glymphatic system by visual circuit activation alleviates memory impairment and apathy in a mouse model of Alzheimer’s disease Nature Communications |
| title | Modulation of glymphatic system by visual circuit activation alleviates memory impairment and apathy in a mouse model of Alzheimer’s disease |
| title_full | Modulation of glymphatic system by visual circuit activation alleviates memory impairment and apathy in a mouse model of Alzheimer’s disease |
| title_fullStr | Modulation of glymphatic system by visual circuit activation alleviates memory impairment and apathy in a mouse model of Alzheimer’s disease |
| title_full_unstemmed | Modulation of glymphatic system by visual circuit activation alleviates memory impairment and apathy in a mouse model of Alzheimer’s disease |
| title_short | Modulation of glymphatic system by visual circuit activation alleviates memory impairment and apathy in a mouse model of Alzheimer’s disease |
| title_sort | modulation of glymphatic system by visual circuit activation alleviates memory impairment and apathy in a mouse model of alzheimer s disease |
| url | https://doi.org/10.1038/s41467-024-55678-w |
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