Role of aquaporin-4 polarization in extracellular solute clearance

Abstract Waste from the brain has been shown to be cleared via the perivascular spaces through the so-called glymphatic system. According to this model the cerebrospinal fluid (CSF) enters the brain in perivascular spaces of arteries, crosses the astrocyte endfoot layer, flows through the parenchyma...
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Autor*in:	Bojarskaite, Laura [verfasserIn] Nafari, Sahar Ravnanger, Anne Katrine Frey, Mina Martine Skauli, Nadia Åbjørsbråten, Knut Sindre Roth, Lena Catherine Amiry-Moghaddam, Mahmood Nagelhus, Erlend A. Ottersen, Ole Petter Bogen, Inger Lise Thoren, Anna E. Enger, Rune

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2024

Schlagwörter:	AQP4 Glymphatic Waste clearance Astrocyte Glia Syntrophin Dystrophin

Anmerkung:	© The Author(s) 2024

Übergeordnetes Werk:	Enthalten in: Fluids and barriers of the CNS - BioMed Central, 2011, 21(2024), 1 vom: 26. März
Übergeordnetes Werk:	volume:21 ; year:2024 ; number:1 ; day:26 ; month:03

Links:	Volltext

DOI / URN:	10.1186/s12987-024-00527-7

Katalog-ID:	SPR055309992

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allfields	10.1186/s12987-024-00527-7 doi (DE-627)SPR055309992 (SPR)s12987-024-00527-7-e DE-627 ger DE-627 rakwb eng 610 VZ Bojarskaite, Laura verfasserin aut Role of aquaporin-4 polarization in extracellular solute clearance 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 Abstract Waste from the brain has been shown to be cleared via the perivascular spaces through the so-called glymphatic system. According to this model the cerebrospinal fluid (CSF) enters the brain in perivascular spaces of arteries, crosses the astrocyte endfoot layer, flows through the parenchyma collecting waste that is subsequently drained along veins. Glymphatic clearance is dependent on astrocytic aquaporin-4 (AQP4) water channels that are highly enriched in the endfeet. Even though the polarized expression of AQP4 in endfeet is thought to be of crucial importance for glymphatic CSF influx, its role in extracellular solute clearance has only been evaluated using non-quantitative fluorescence measurements. Here we have quantitatively evaluated clearance of intrastriatally infused small and large radioactively labeled solutes in mice lacking AQP4 (Aqp4–/–) or lacking the endfoot pool of AQP4 (Snta1–/–). We confirm that Aqp4–/– mice show reduced clearance of both small and large extracellular solutes. Moreover, we find that the Snta1–/– mice have reduced clearance only for the 500 kDa [3H]dextran, but not 0.18 kDa [3H]mannitol suggesting that polarization of AQP4 to the endfeet is primarily important for clearance of large, but not small molecules. Lastly, we observed that clearance of 500 kDa [3H]dextran increased with age in adult mice. Based on our quantitative measurements, we confirm that presence of AQP4 is important for clearance of extracellular solutes, while the perivascular AQP4 localization seems to have a greater impact on clearance of large versus small molecules. AQP4 (dpeaa)DE-He213 Glymphatic (dpeaa)DE-He213 Waste clearance (dpeaa)DE-He213 Astrocyte (dpeaa)DE-He213 Glia (dpeaa)DE-He213 Syntrophin (dpeaa)DE-He213 Dystrophin (dpeaa)DE-He213 Nafari, Sahar aut Ravnanger, Anne Katrine aut Frey, Mina Martine aut Skauli, Nadia aut Åbjørsbråten, Knut Sindre aut Roth, Lena Catherine aut Amiry-Moghaddam, Mahmood aut Nagelhus, Erlend A. aut Ottersen, Ole Petter aut Bogen, Inger Lise aut Thoren, Anna E. aut Enger, Rune aut Enthalten in Fluids and barriers of the CNS BioMed Central, 2011 21(2024), 1 vom: 26. März Online-Ressource (DE-627)647306441 (DE-600)2595406-4 (DE-576)337894132 2045-8118 nnns volume:21 year:2024 number:1 day:26 month:03 https://dx.doi.org/10.1186/s12987-024-00527-7 kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 21 2024 1 26 03
spelling	10.1186/s12987-024-00527-7 doi (DE-627)SPR055309992 (SPR)s12987-024-00527-7-e DE-627 ger DE-627 rakwb eng 610 VZ Bojarskaite, Laura verfasserin aut Role of aquaporin-4 polarization in extracellular solute clearance 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 Abstract Waste from the brain has been shown to be cleared via the perivascular spaces through the so-called glymphatic system. According to this model the cerebrospinal fluid (CSF) enters the brain in perivascular spaces of arteries, crosses the astrocyte endfoot layer, flows through the parenchyma collecting waste that is subsequently drained along veins. Glymphatic clearance is dependent on astrocytic aquaporin-4 (AQP4) water channels that are highly enriched in the endfeet. Even though the polarized expression of AQP4 in endfeet is thought to be of crucial importance for glymphatic CSF influx, its role in extracellular solute clearance has only been evaluated using non-quantitative fluorescence measurements. Here we have quantitatively evaluated clearance of intrastriatally infused small and large radioactively labeled solutes in mice lacking AQP4 (Aqp4–/–) or lacking the endfoot pool of AQP4 (Snta1–/–). We confirm that Aqp4–/– mice show reduced clearance of both small and large extracellular solutes. Moreover, we find that the Snta1–/– mice have reduced clearance only for the 500 kDa [3H]dextran, but not 0.18 kDa [3H]mannitol suggesting that polarization of AQP4 to the endfeet is primarily important for clearance of large, but not small molecules. Lastly, we observed that clearance of 500 kDa [3H]dextran increased with age in adult mice. Based on our quantitative measurements, we confirm that presence of AQP4 is important for clearance of extracellular solutes, while the perivascular AQP4 localization seems to have a greater impact on clearance of large versus small molecules. AQP4 (dpeaa)DE-He213 Glymphatic (dpeaa)DE-He213 Waste clearance (dpeaa)DE-He213 Astrocyte (dpeaa)DE-He213 Glia (dpeaa)DE-He213 Syntrophin (dpeaa)DE-He213 Dystrophin (dpeaa)DE-He213 Nafari, Sahar aut Ravnanger, Anne Katrine aut Frey, Mina Martine aut Skauli, Nadia aut Åbjørsbråten, Knut Sindre aut Roth, Lena Catherine aut Amiry-Moghaddam, Mahmood aut Nagelhus, Erlend A. aut Ottersen, Ole Petter aut Bogen, Inger Lise aut Thoren, Anna E. aut Enger, Rune aut Enthalten in Fluids and barriers of the CNS BioMed Central, 2011 21(2024), 1 vom: 26. März Online-Ressource (DE-627)647306441 (DE-600)2595406-4 (DE-576)337894132 2045-8118 nnns volume:21 year:2024 number:1 day:26 month:03 https://dx.doi.org/10.1186/s12987-024-00527-7 kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 21 2024 1 26 03
allfields_unstemmed	10.1186/s12987-024-00527-7 doi (DE-627)SPR055309992 (SPR)s12987-024-00527-7-e DE-627 ger DE-627 rakwb eng 610 VZ Bojarskaite, Laura verfasserin aut Role of aquaporin-4 polarization in extracellular solute clearance 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 Abstract Waste from the brain has been shown to be cleared via the perivascular spaces through the so-called glymphatic system. According to this model the cerebrospinal fluid (CSF) enters the brain in perivascular spaces of arteries, crosses the astrocyte endfoot layer, flows through the parenchyma collecting waste that is subsequently drained along veins. Glymphatic clearance is dependent on astrocytic aquaporin-4 (AQP4) water channels that are highly enriched in the endfeet. Even though the polarized expression of AQP4 in endfeet is thought to be of crucial importance for glymphatic CSF influx, its role in extracellular solute clearance has only been evaluated using non-quantitative fluorescence measurements. Here we have quantitatively evaluated clearance of intrastriatally infused small and large radioactively labeled solutes in mice lacking AQP4 (Aqp4–/–) or lacking the endfoot pool of AQP4 (Snta1–/–). We confirm that Aqp4–/– mice show reduced clearance of both small and large extracellular solutes. Moreover, we find that the Snta1–/– mice have reduced clearance only for the 500 kDa [3H]dextran, but not 0.18 kDa [3H]mannitol suggesting that polarization of AQP4 to the endfeet is primarily important for clearance of large, but not small molecules. Lastly, we observed that clearance of 500 kDa [3H]dextran increased with age in adult mice. Based on our quantitative measurements, we confirm that presence of AQP4 is important for clearance of extracellular solutes, while the perivascular AQP4 localization seems to have a greater impact on clearance of large versus small molecules. AQP4 (dpeaa)DE-He213 Glymphatic (dpeaa)DE-He213 Waste clearance (dpeaa)DE-He213 Astrocyte (dpeaa)DE-He213 Glia (dpeaa)DE-He213 Syntrophin (dpeaa)DE-He213 Dystrophin (dpeaa)DE-He213 Nafari, Sahar aut Ravnanger, Anne Katrine aut Frey, Mina Martine aut Skauli, Nadia aut Åbjørsbråten, Knut Sindre aut Roth, Lena Catherine aut Amiry-Moghaddam, Mahmood aut Nagelhus, Erlend A. aut Ottersen, Ole Petter aut Bogen, Inger Lise aut Thoren, Anna E. aut Enger, Rune aut Enthalten in Fluids and barriers of the CNS BioMed Central, 2011 21(2024), 1 vom: 26. März Online-Ressource (DE-627)647306441 (DE-600)2595406-4 (DE-576)337894132 2045-8118 nnns volume:21 year:2024 number:1 day:26 month:03 https://dx.doi.org/10.1186/s12987-024-00527-7 kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 21 2024 1 26 03
allfieldsGer	10.1186/s12987-024-00527-7 doi (DE-627)SPR055309992 (SPR)s12987-024-00527-7-e DE-627 ger DE-627 rakwb eng 610 VZ Bojarskaite, Laura verfasserin aut Role of aquaporin-4 polarization in extracellular solute clearance 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 Abstract Waste from the brain has been shown to be cleared via the perivascular spaces through the so-called glymphatic system. According to this model the cerebrospinal fluid (CSF) enters the brain in perivascular spaces of arteries, crosses the astrocyte endfoot layer, flows through the parenchyma collecting waste that is subsequently drained along veins. Glymphatic clearance is dependent on astrocytic aquaporin-4 (AQP4) water channels that are highly enriched in the endfeet. Even though the polarized expression of AQP4 in endfeet is thought to be of crucial importance for glymphatic CSF influx, its role in extracellular solute clearance has only been evaluated using non-quantitative fluorescence measurements. Here we have quantitatively evaluated clearance of intrastriatally infused small and large radioactively labeled solutes in mice lacking AQP4 (Aqp4–/–) or lacking the endfoot pool of AQP4 (Snta1–/–). We confirm that Aqp4–/– mice show reduced clearance of both small and large extracellular solutes. Moreover, we find that the Snta1–/– mice have reduced clearance only for the 500 kDa [3H]dextran, but not 0.18 kDa [3H]mannitol suggesting that polarization of AQP4 to the endfeet is primarily important for clearance of large, but not small molecules. Lastly, we observed that clearance of 500 kDa [3H]dextran increased with age in adult mice. Based on our quantitative measurements, we confirm that presence of AQP4 is important for clearance of extracellular solutes, while the perivascular AQP4 localization seems to have a greater impact on clearance of large versus small molecules. AQP4 (dpeaa)DE-He213 Glymphatic (dpeaa)DE-He213 Waste clearance (dpeaa)DE-He213 Astrocyte (dpeaa)DE-He213 Glia (dpeaa)DE-He213 Syntrophin (dpeaa)DE-He213 Dystrophin (dpeaa)DE-He213 Nafari, Sahar aut Ravnanger, Anne Katrine aut Frey, Mina Martine aut Skauli, Nadia aut Åbjørsbråten, Knut Sindre aut Roth, Lena Catherine aut Amiry-Moghaddam, Mahmood aut Nagelhus, Erlend A. aut Ottersen, Ole Petter aut Bogen, Inger Lise aut Thoren, Anna E. aut Enger, Rune aut Enthalten in Fluids and barriers of the CNS BioMed Central, 2011 21(2024), 1 vom: 26. März Online-Ressource (DE-627)647306441 (DE-600)2595406-4 (DE-576)337894132 2045-8118 nnns volume:21 year:2024 number:1 day:26 month:03 https://dx.doi.org/10.1186/s12987-024-00527-7 kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 21 2024 1 26 03
allfieldsSound	10.1186/s12987-024-00527-7 doi (DE-627)SPR055309992 (SPR)s12987-024-00527-7-e DE-627 ger DE-627 rakwb eng 610 VZ Bojarskaite, Laura verfasserin aut Role of aquaporin-4 polarization in extracellular solute clearance 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 Abstract Waste from the brain has been shown to be cleared via the perivascular spaces through the so-called glymphatic system. According to this model the cerebrospinal fluid (CSF) enters the brain in perivascular spaces of arteries, crosses the astrocyte endfoot layer, flows through the parenchyma collecting waste that is subsequently drained along veins. Glymphatic clearance is dependent on astrocytic aquaporin-4 (AQP4) water channels that are highly enriched in the endfeet. Even though the polarized expression of AQP4 in endfeet is thought to be of crucial importance for glymphatic CSF influx, its role in extracellular solute clearance has only been evaluated using non-quantitative fluorescence measurements. Here we have quantitatively evaluated clearance of intrastriatally infused small and large radioactively labeled solutes in mice lacking AQP4 (Aqp4–/–) or lacking the endfoot pool of AQP4 (Snta1–/–). We confirm that Aqp4–/– mice show reduced clearance of both small and large extracellular solutes. Moreover, we find that the Snta1–/– mice have reduced clearance only for the 500 kDa [3H]dextran, but not 0.18 kDa [3H]mannitol suggesting that polarization of AQP4 to the endfeet is primarily important for clearance of large, but not small molecules. Lastly, we observed that clearance of 500 kDa [3H]dextran increased with age in adult mice. Based on our quantitative measurements, we confirm that presence of AQP4 is important for clearance of extracellular solutes, while the perivascular AQP4 localization seems to have a greater impact on clearance of large versus small molecules. AQP4 (dpeaa)DE-He213 Glymphatic (dpeaa)DE-He213 Waste clearance (dpeaa)DE-He213 Astrocyte (dpeaa)DE-He213 Glia (dpeaa)DE-He213 Syntrophin (dpeaa)DE-He213 Dystrophin (dpeaa)DE-He213 Nafari, Sahar aut Ravnanger, Anne Katrine aut Frey, Mina Martine aut Skauli, Nadia aut Åbjørsbråten, Knut Sindre aut Roth, Lena Catherine aut Amiry-Moghaddam, Mahmood aut Nagelhus, Erlend A. aut Ottersen, Ole Petter aut Bogen, Inger Lise aut Thoren, Anna E. aut Enger, Rune aut Enthalten in Fluids and barriers of the CNS BioMed Central, 2011 21(2024), 1 vom: 26. März Online-Ressource (DE-627)647306441 (DE-600)2595406-4 (DE-576)337894132 2045-8118 nnns volume:21 year:2024 number:1 day:26 month:03 https://dx.doi.org/10.1186/s12987-024-00527-7 kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 21 2024 1 26 03
language	English
source	Enthalten in Fluids and barriers of the CNS 21(2024), 1 vom: 26. März volume:21 year:2024 number:1 day:26 month:03
sourceStr	Enthalten in Fluids and barriers of the CNS 21(2024), 1 vom: 26. März volume:21 year:2024 number:1 day:26 month:03
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	AQP4 Glymphatic Waste clearance Astrocyte Glia Syntrophin Dystrophin
dewey-raw	610
isfreeaccess_bool	true
container_title	Fluids and barriers of the CNS
authorswithroles_txt_mv	Bojarskaite, Laura @@aut@@ Nafari, Sahar @@aut@@ Ravnanger, Anne Katrine @@aut@@ Frey, Mina Martine @@aut@@ Skauli, Nadia @@aut@@ Åbjørsbråten, Knut Sindre @@aut@@ Roth, Lena Catherine @@aut@@ Amiry-Moghaddam, Mahmood @@aut@@ Nagelhus, Erlend A. @@aut@@ Ottersen, Ole Petter @@aut@@ Bogen, Inger Lise @@aut@@ Thoren, Anna E. @@aut@@ Enger, Rune @@aut@@
publishDateDaySort_date	2024-03-26T00:00:00Z
hierarchy_top_id	647306441
dewey-sort	3610
id	SPR055309992
language_de	englisch
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author	Bojarskaite, Laura
spellingShingle	Bojarskaite, Laura ddc 610 misc AQP4 misc Glymphatic misc Waste clearance misc Astrocyte misc Glia misc Syntrophin misc Dystrophin Role of aquaporin-4 polarization in extracellular solute clearance
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topic_title	610 VZ Role of aquaporin-4 polarization in extracellular solute clearance AQP4 (dpeaa)DE-He213 Glymphatic (dpeaa)DE-He213 Waste clearance (dpeaa)DE-He213 Astrocyte (dpeaa)DE-He213 Glia (dpeaa)DE-He213 Syntrophin (dpeaa)DE-He213 Dystrophin (dpeaa)DE-He213
topic	ddc 610 misc AQP4 misc Glymphatic misc Waste clearance misc Astrocyte misc Glia misc Syntrophin misc Dystrophin
topic_unstemmed	ddc 610 misc AQP4 misc Glymphatic misc Waste clearance misc Astrocyte misc Glia misc Syntrophin misc Dystrophin
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title	Role of aquaporin-4 polarization in extracellular solute clearance
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title_full	Role of aquaporin-4 polarization in extracellular solute clearance
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author_browse	Bojarskaite, Laura Nafari, Sahar Ravnanger, Anne Katrine Frey, Mina Martine Skauli, Nadia Åbjørsbråten, Knut Sindre Roth, Lena Catherine Amiry-Moghaddam, Mahmood Nagelhus, Erlend A. Ottersen, Ole Petter Bogen, Inger Lise Thoren, Anna E. Enger, Rune
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title_sort	role of aquaporin-4 polarization in extracellular solute clearance
title_auth	Role of aquaporin-4 polarization in extracellular solute clearance
abstract	Abstract Waste from the brain has been shown to be cleared via the perivascular spaces through the so-called glymphatic system. According to this model the cerebrospinal fluid (CSF) enters the brain in perivascular spaces of arteries, crosses the astrocyte endfoot layer, flows through the parenchyma collecting waste that is subsequently drained along veins. Glymphatic clearance is dependent on astrocytic aquaporin-4 (AQP4) water channels that are highly enriched in the endfeet. Even though the polarized expression of AQP4 in endfeet is thought to be of crucial importance for glymphatic CSF influx, its role in extracellular solute clearance has only been evaluated using non-quantitative fluorescence measurements. Here we have quantitatively evaluated clearance of intrastriatally infused small and large radioactively labeled solutes in mice lacking AQP4 (Aqp4–/–) or lacking the endfoot pool of AQP4 (Snta1–/–). We confirm that Aqp4–/– mice show reduced clearance of both small and large extracellular solutes. Moreover, we find that the Snta1–/– mice have reduced clearance only for the 500 kDa [3H]dextran, but not 0.18 kDa [3H]mannitol suggesting that polarization of AQP4 to the endfeet is primarily important for clearance of large, but not small molecules. Lastly, we observed that clearance of 500 kDa [3H]dextran increased with age in adult mice. Based on our quantitative measurements, we confirm that presence of AQP4 is important for clearance of extracellular solutes, while the perivascular AQP4 localization seems to have a greater impact on clearance of large versus small molecules. © The Author(s) 2024
abstractGer	Abstract Waste from the brain has been shown to be cleared via the perivascular spaces through the so-called glymphatic system. According to this model the cerebrospinal fluid (CSF) enters the brain in perivascular spaces of arteries, crosses the astrocyte endfoot layer, flows through the parenchyma collecting waste that is subsequently drained along veins. Glymphatic clearance is dependent on astrocytic aquaporin-4 (AQP4) water channels that are highly enriched in the endfeet. Even though the polarized expression of AQP4 in endfeet is thought to be of crucial importance for glymphatic CSF influx, its role in extracellular solute clearance has only been evaluated using non-quantitative fluorescence measurements. Here we have quantitatively evaluated clearance of intrastriatally infused small and large radioactively labeled solutes in mice lacking AQP4 (Aqp4–/–) or lacking the endfoot pool of AQP4 (Snta1–/–). We confirm that Aqp4–/– mice show reduced clearance of both small and large extracellular solutes. Moreover, we find that the Snta1–/– mice have reduced clearance only for the 500 kDa [3H]dextran, but not 0.18 kDa [3H]mannitol suggesting that polarization of AQP4 to the endfeet is primarily important for clearance of large, but not small molecules. Lastly, we observed that clearance of 500 kDa [3H]dextran increased with age in adult mice. Based on our quantitative measurements, we confirm that presence of AQP4 is important for clearance of extracellular solutes, while the perivascular AQP4 localization seems to have a greater impact on clearance of large versus small molecules. © The Author(s) 2024
abstract_unstemmed	Abstract Waste from the brain has been shown to be cleared via the perivascular spaces through the so-called glymphatic system. According to this model the cerebrospinal fluid (CSF) enters the brain in perivascular spaces of arteries, crosses the astrocyte endfoot layer, flows through the parenchyma collecting waste that is subsequently drained along veins. Glymphatic clearance is dependent on astrocytic aquaporin-4 (AQP4) water channels that are highly enriched in the endfeet. Even though the polarized expression of AQP4 in endfeet is thought to be of crucial importance for glymphatic CSF influx, its role in extracellular solute clearance has only been evaluated using non-quantitative fluorescence measurements. Here we have quantitatively evaluated clearance of intrastriatally infused small and large radioactively labeled solutes in mice lacking AQP4 (Aqp4–/–) or lacking the endfoot pool of AQP4 (Snta1–/–). We confirm that Aqp4–/– mice show reduced clearance of both small and large extracellular solutes. Moreover, we find that the Snta1–/– mice have reduced clearance only for the 500 kDa [3H]dextran, but not 0.18 kDa [3H]mannitol suggesting that polarization of AQP4 to the endfeet is primarily important for clearance of large, but not small molecules. Lastly, we observed that clearance of 500 kDa [3H]dextran increased with age in adult mice. Based on our quantitative measurements, we confirm that presence of AQP4 is important for clearance of extracellular solutes, while the perivascular AQP4 localization seems to have a greater impact on clearance of large versus small molecules. © The Author(s) 2024
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title_short	Role of aquaporin-4 polarization in extracellular solute clearance
url	https://dx.doi.org/10.1186/s12987-024-00527-7
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author2	Nafari, Sahar Ravnanger, Anne Katrine Frey, Mina Martine Skauli, Nadia Åbjørsbråten, Knut Sindre Roth, Lena Catherine Amiry-Moghaddam, Mahmood Nagelhus, Erlend A. Ottersen, Ole Petter Bogen, Inger Lise Thoren, Anna E. Enger, Rune
author2Str	Nafari, Sahar Ravnanger, Anne Katrine Frey, Mina Martine Skauli, Nadia Åbjørsbråten, Knut Sindre Roth, Lena Catherine Amiry-Moghaddam, Mahmood Nagelhus, Erlend A. Ottersen, Ole Petter Bogen, Inger Lise Thoren, Anna E. Enger, Rune
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Role of aquaporin-4 polarization in extracellular solute clearance

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