Aquaporin-4 dependent glymphatic solute transport in rodent brain
| Autor: | Humberto Mestre, Benjamin T. Kress, Wenyan Zou, Tinglin Pu, Giridhar Murlidharan, Ruth M. Castellanos Rivera, Matthew J. Simon, Martin M. Pike, Benjamin A Plog, Anna L. R. Xavier, Alexander S. Thrane, Iben Lundgaard, John H. Thomas, Ming Xiao, Aravind Asokan, Jeffrey J. Miff, Maiken Nedergaard |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0303 health sciences
Rodent biology Metabolite Fluid transport Cell biology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cerebrospinal fluid Aquaporin 4 chemistry Interstitial fluid biology.animal Glymphatic system Efflux sense organs 030217 neurology & neurosurgery 030304 developmental biology |
| DOI: | 10.1101/216499 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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