RT Journal Article
SR Electronic
T1 Aquaporin-4 dependent glymphatic solute transport in rodent brain
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 216499
DO 10.1101/216499
A1 Humberto Mestre
A1 Benjamin T. Kress
A1 Wenyan Zou
A1 Tinglin Pu
A1 Giridhar Murlidharan
A1 Ruth M. Castellanos Rivera
A1 Matthew J. Simon
A1 Martin M. Pike
A1 Benjamin A Plog
A1 Anna L. R. Xavier
A1 Alexander S. Thrane
A1 Iben Lundgaard
A1 John H. Thomas
A1 Ming Xiao
A1 Aravind Asokan
A1 Jeffrey J. Miff
A1 Maiken Nedergaard
YR 2017
UL http://biorxiv.org/content/early/2017/11/09/216499.abstract
AB The glymphatic system is a brain-wide metabolite clearance pathway, impairment of which in post-traumatic and ischemic brain or healthy aging is proposed to contribute to intracerebral accumulation of amyloid-β and tau proteins. Glymphatic perivascular influx of cerebrospinal fluid (CSF) depends upon the expression and perivascular localization of the astroglial water channel aquaporin-4 (AQP4). Prompted by a recent publication that failed to find an effect of Aqp4 knockout on perivascular CSF tracer influx and interstitial fluid (ISF) tracer dispersion, four independent research groups have herein re-examined the importance of Aqp4 in glymphatic fluid transport. We concur in finding that CSF tracer influx, as well as fluorescently-tagged amyloid-β efflux, are significantly faster in wild-type mice than in three different transgenic lines featuring disruption of the Aqp4 gene and one line in which AQP4 expression lacks the critical perivascular localization (Snta1 knockout). These data validate the role of AQP4 in supporting fluid and solute transport and efflux in brain in accordance with the glymphatic system model.