eLife (Dec 2018)
Aquaporin-4-dependent glymphatic solute transport in the rodent brain
- Humberto Mestre,
- Lauren M Hablitz,
- Anna LR Xavier,
- Weixi Feng,
- Wenyan Zou,
- Tinglin Pu,
- Hiromu Monai,
- Giridhar Murlidharan,
- Ruth M Castellanos Rivera,
- Matthew J Simon,
- Martin M Pike,
- Virginia Plá,
- Ting Du,
- Benjamin T Kress,
- Xiaowen Wang,
- Benjamin A Plog,
- Alexander S Thrane,
- Iben Lundgaard,
- Yoichiro Abe,
- Masato Yasui,
- John H Thomas,
- Ming Xiao,
- Hajime Hirase,
- Aravind Asokan,
- Jeffrey J Iliff,
- Maiken Nedergaard
Affiliations
- Humberto Mestre
- ORCiD
- Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, United States
- Lauren M Hablitz
- ORCiD
- Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, United States
- Anna LR Xavier
- Center for Translational Neuromedicine, Faculty of Medical and Health Sciences, University of Copenhagen, Copenhagen, Denmark
- Weixi Feng
- Jiangsu Province Key Laboratory of Neurodegeneration, Center for Global Health, Nanjing Medical University, Nanjing, China
- Wenyan Zou
- Jiangsu Province Key Laboratory of Neurodegeneration, Center for Global Health, Nanjing Medical University, Nanjing, China
- Tinglin Pu
- Jiangsu Province Key Laboratory of Neurodegeneration, Center for Global Health, Nanjing Medical University, Nanjing, China
- Hiromu Monai
- ORCiD
- RIKEN Center for Brain Science, Wako, Japan; Ochanomizu University, Tokyo, Japan
- Giridhar Murlidharan
- Gene Therapy Center, The University of North Carolina, Chapel Hill, United States
- Ruth M Castellanos Rivera
- Gene Therapy Center, The University of North Carolina, Chapel Hill, United States
- Matthew J Simon
- Department of Anesthesiology and Perioperative Medicine, Oregon Health and Science University, Portland, United States
- Martin M Pike
- Advanced Imaging Research Center, Oregon Health and Science University, Portland, United States
- Virginia Plá
- ORCiD
- Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, United States
- Ting Du
- Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, United States
- Benjamin T Kress
- Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, United States
- Xiaowen Wang
- RIKEN Center for Brain Science, Wako, Japan
- Benjamin A Plog
- Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, United States
- Alexander S Thrane
- Center for Translational Neuromedicine, Faculty of Medical and Health Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Ophthalmology, Haukeland University Hospital, Bergen, Norway
- Iben Lundgaard
- Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, United States; Department of Experimental Medical Science, Lund University, Lund, Sweden; Wallenberg Center for Molecular Medicine, Lund University, Lund, Sweden
- Yoichiro Abe
- ORCiD
- Department of Pharmacology,School of Medicine, Keio University, Tokyo, Japan
- Masato Yasui
- Department of Pharmacology,School of Medicine, Keio University, Tokyo, Japan
- John H Thomas
- Department of Mechanical Engineering, University of Rochester, Rochester, United States; Department of Physics and Astronomy, University of Rochester, Rochester, United States
- Ming Xiao
- Jiangsu Province Key Laboratory of Neurodegeneration, Center for Global Health, Nanjing Medical University, Nanjing, China
- Hajime Hirase
- ORCiD
- RIKEN Center for Brain Science, Wako, Japan; Brain and Body System Science Institute, Saitama University, Saitama, Japan
- Aravind Asokan
- Gene Therapy Center, The University of North Carolina, Chapel Hill, United States; Department of Molecular Genetics and Microbiology, Duke University School of Medicine, North Carolina, United States; Department of Surgery, Duke University School of Medicine, Durham, United States
- Jeffrey J Iliff
- Department of Anesthesiology and Perioperative Medicine, Oregon Health and Science University, Portland, United States; Knight Cardiovascular Institute, Oregon Health and Science University, Portland, United States
- Maiken Nedergaard
- ORCiD
- Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, United States; Center for Translational Neuromedicine, Faculty of Medical and Health Sciences, University of Copenhagen, Copenhagen, Denmark
- DOI
- https://doi.org/10.7554/eLife.40070
- Journal volume & issue
-
Vol. 7
Abstract
The glymphatic system is a brain-wide clearance pathway; its impairment contributes to the accumulation of amyloid-β. 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.
Keywords
