淋巴系统
γ-氨基丁酸受体
水通道蛋白4
脑脊液
化学
γ-氨基丁酸
CTB公司
加巴能
刺激
荷包牡丹碱
细胞生物学
神经科学
受体
生物化学
神经传递
生物
变质塑性
作者
Chang-Chieh Wu,Qun Zhang,Yiwei Feng,Ni Zhang,Q Liu,Zi-tong Ou,Tuo Lin,Qi Ding,Ge Li,Zhong Pei,Yue Lan,Gelin Xu
摘要
The glymphatic system is a newly discovered perivascular network where cerebrospinal fluid mixes with interstitial fluid, facilitating clearance of protein solutes and metabolic waste from the parenchyma. The process is strictly dependent on water channel aquaporin-4 (AQP4) expressed on the perivascular astrocytic end-feet. Various factors, such as noradrenaline levels related to the arousal state, influence clearance efficiency, highlighting the possibility that other neurotransmitters additionally modulate this process. To date, the specific role of γ-aminobutyric acid (GABA) in the glymphatic system remains unknown. We used C57BL/6J mice to observe the regulatory effect of GABA on glymphatic pathway by administering a cerebrospinal fluid tracer containing GABA or its GABAA receptor (GABAA R) antagonist through cisterna magna injection. Then, we employed an AQP4 knockout mouse model to explore the regulatory effects of GABA on glymphatic drainage and further study whether transcranial magnetic stimulation-continuous theta burst stimulation (cTBS) could regulate the glymphatic pathway through the GABA system. Our data showed that GABA promotes glymphatic clearance in an AQP4-dependent manner by activating the GABAA R. Furthermore, cTBS was found to modulate the glymphatic pathway by activating the GABA system. Accordingly, we propose that regulating the GABA system by cTBS could modulate glymphatic clearance and provide new insight for clinical prevention and treatment of abnormal protein deposition-related diseases.
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