Glutamate and γ-aminobutyric acid differentially modulate glymphatic clearance of amyloid β through pulsation- and aquaporin-4 dependent mechanisms
Glutamate and γ-aminobutyric acid differentially modulate glymphatic clearance of amyloid β through pulsation- and aquaporin-4 dependent mechanisms
Abstract The glymphatic system contributes to a large proportion of brain waste clearance, including removal of amyloid β (Aβ). We have demonstrated that glutamate and γ-aminobutyric acid (GABA) influence glymphatic clearance through distinct mechanisms whereby GABA exerts modulatory effects in an aquaporin-4 (AQP4)-dependent manner while the actions of glutamate are pulsation-dependent. The efficacy of GABA and glutamate in alleviating Aβ in APP-PS1 and Angiotensin-II (Ang-II) induced hypertension mouse models was further evaluated. Notably, increasing GABA or inhibiting glutamate levels led to reduced binding of Aβ to pre-labeled plaques to similar extents in APP-PS1 mice while GABA appeared more efficient in Aβ clearance in hypertensive animals than the glutamate inhibitor. Our findings support the modulation of neurotransmitters that influence the glymphatic pathway via distinct mechanisms as a potentially effective therapeutic strategy for clearance of Aβ deposits from the brain.
Feng Yi-wei、Zhang Qun、Lan Yue、Xu Guang-qing、Pei Zhong、Liang Feng-yin、Wu Cheng
Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, The First Affiliated Hospital, Sun Yat-sen UniversityGuangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, The First Affiliated Hospital, Sun Yat-sen UniversityDepartment of Rehabilitation Medicine, Guangzhou First People?ˉs Hospital, School of Medicine, South China University of TechnologyDepartment of Rehabilitation Medicine, Beijing Tiantan Hospital, Capital Medical UniversityGuangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, The First Affiliated Hospital, Sun Yat-sen UniversityGuangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, The First Affiliated Hospital, Sun Yat-sen UniversityDepartment of Rehabilitation Medicine, Guangzhou First People?ˉs Hospital, School of Medicine, South China University of Technology
基础医学神经病学、精神病学生理学
brainpulsationaquaporin-4GlutamateGABAwaste removal
Feng Yi-wei,Zhang Qun,Lan Yue,Xu Guang-qing,Pei Zhong,Liang Feng-yin,Wu Cheng.Glutamate and γ-aminobutyric acid differentially modulate glymphatic clearance of amyloid β through pulsation- and aquaporin-4 dependent mechanisms[EB/OL].(2025-03-28)[2025-05-13].https://www.biorxiv.org/content/10.1101/2020.01.31.928481.点此复制
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