Aquaporin-4-dependent glymphatic solute transport in the rodent brain
Aquaporin-4-dependent glymphatic solute transport in the rodent brain
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DOI：
10.7554/elife.40070
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发表时间：
2018-12-18
期刊：
影响因子：
7.7
通讯作者：
Nedergaard, Maiken
中科院分区：
文献类型：
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作者：
Mestre, Humberto;Hablitz, Lauren M.;Nedergaard, Maiken
类淋巴系统是一条全脑清除途径；它的损伤导致β-淀粉样蛋白的积累。脑脊液 (CSF) 的流入取决于星形胶质细胞水通道水通道蛋白 4 (AQP4) 的表达和血管周围定位。由于最近未能发现 Aqp4 敲除 (KO) 对脑脊液和间质液 (ISF) 示踪剂运输的影响，五个小组重新研究了 AQP4 在类淋巴运输中的重要性。我们一致认为，野生型小鼠的脑脊液流入量高于四种不同的 Aqp4 KO 系和一种缺乏血管周围 AQP4 (Snta1 KO) 的系。所有研究的荟萃分析表明，与对照组相比，KO 小鼠和大鼠的示踪剂转运显着减少。荟萃回归表明麻醉、年龄和示踪剂输送可以解释相反的结果。我们还报告说，纹状体内注射会抑制类淋巴功能。这验证了 AQP4 的作用，并表明类淋巴系统研究必须避免使用侵入性操作。
The glymphatic system is a brain-wide clearance pathway; its impairment contributes to the accumulation of amyloid-beta. Influx of cerebrospinal fluid (CSF) depends upon the expression and perivascular localization of the astroglial water channel aquaporin-4 (AQP4). Prompted by a recent failure to find an effect of Aqp4 knock-out (KO) on CSF and interstitial fluid (ISF) tracer transport, five groups re-examined the importance of AQP4 in glymphatic transport. We concur that CSF influx is higher in wild-type mice than in four different Aqp4 KO lines and in one line that lacks perivascular AQP4 (Snta1 KO). Meta-analysis of all studies demonstrated a significant decrease in tracer transport in KO mice and rats compared to controls. Meta-regression indicated that anesthesia, age, and tracer delivery explain the opposing results. We also report that intrastriatal injections suppress glymphatic function. This validates the role of AQP4 and shows that glymphatic studies must avoid the use of invasive procedures.