Aquaporin-4-dependent glymphatic solute transport in the rodent brain

被引：429

作者：

Mestre, Humberto ^{[1
]}

Hablitz, Lauren M. ^{[1
]}

Xavier, Anna L. R. ^{[2
]}

Feng, Weixi ^{[3
]}

Zou, Wenyan ^{[3
]}

Pu, Tinglin ^{[3
]}

Monai, Hiromu ^{[4
,5
]}

Murlidharan, Giridhar ^{[6
]}

Rivera, Ruth M. Castellanos ^{[6
]}

Simon, Matthew J. ^{[7
]}

Pike, Martin M. ^{[8
]}

Pla, Virginia ^{[1
]}

Du, Ting ^{[1
]}

Kress, Benjamin T. ^{[1
]}

Wang, Xiaowen ^{[4
]}

Plog, Benjamin A. ^{[1
]}

Thrane, Alexander S. ^{[2
,9
]}

Lundgaard, Iben ^{[1
,10
,11
]}

Abe, Yoichiro ^{[12
]}

Yasui, Masato ^{[12
]}

Thomas, John H. ^{[13
,14
]}

Xiao, Ming ^{[3
]}

Hirase, Hajime ^{[4
,15
]}

Asokan, Aravind ^{[6
,16
,17
]}

Iliff, Jeffrey J. ^{[7
,18
]}

Nedergaard, Maiken ^{[1
,2
]}

机构：

[1] Univ Rochester, Med Ctr, Ctr Translat Neuromed, Rochester, NY 14627 USA

[2] Univ Copenhagen, Fac Med & Hlth Sci, Ctr Translat Neuromed, Copenhagen, Denmark

[3] Nanjing Med Univ, Ctr Global Hlth, Jiangsu Prov Key Lab Neurodegenerat, Nanjing, Jiangsu, Peoples R China

[4] RIKEN Ctr Brain Sci, Wako, Saitama, Japan

[5] Ochanomizu Univ, Tokyo, Japan

[6] Gene Therapy Ctr, Chapel Hill, NC 27514 USA

[7] Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97201 USA

[8] Oregon Hlth & Sci Univ, Adv Imaging Res Ctr, Portland, OR 97201 USA

[9] Haukeland Hosp, Dept Ophthalmol, Bergen, Norway

[10] Lund Univ, Dept Expt Med Sci, Lund, Sweden

[11] Lund Univ, Wallenberg Ctr Mol Med, Lund, Sweden

[12] Keio Univ, Sch Med, Dept Pharmacol, Tokyo, Japan

[13] Univ Rochester, Dept Mech Engn, Rochester, NY 14627 USA

[14] Univ Rochester, Dept Phys & Astron, Rochester, NY 14627 USA

[15] Saitama Univ, Brain & Body Syst Sci Inst, Saitama, Japan

[16] Duke Univ, Sch Med, Dept Mol Genet & Microbiol, Durham, NC 27706 USA

[17] Duke Univ, Sch Med, Dept Surg, Durham, NC 27706 USA

[18] Oregon Hlth & Sci Univ, Knight Cardiovasc Inst, Portland, OR 97201 USA

来源：

ELIFE | 2018年 / 7卷

基金：

日本学术振兴会; 美国国家卫生研究院;

关键词：

CENTRAL-NERVOUS-SYSTEM; EXTRACELLULAR-SPACE; INTERSTITIAL FLUID; AMYLOID-BETA; CLEARANCE; ANESTHESIA; PATHWAY; IMPAIRMENT; KNOCKOUT; BLOOD;

D O I：

10.7554/eLife.40070

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：31

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