Aquaporins in Nervous System.
Aquaporins
Brain disorders
Nervous system
Journal
Advances in experimental medicine and biology
ISSN: 0065-2598
Titre abrégé: Adv Exp Med Biol
Pays: United States
ID NLM: 0121103
Informations de publication
Date de publication:
2023
2023
Historique:
entrez:
30
1
2023
pubmed:
31
1
2023
medline:
2
2
2023
Statut:
ppublish
Résumé
Aquaporins (AQPs) mediate water flux between the four distinct water compartments in the central nervous system (CNS). In the present chapter, we mainly focus on the expression and function of the nine AQPs expressed in the CNS, which include five members of aquaporin subfamily: AQP1, AQP4, AQP5, AQP6, and AQP8; three members of aquaglyceroporin subfamily: AQP3, AQP7, and AQP9; and one member of superaquaporin subfamily: AQP11. In addition, AQP1, AQP2, and AQP4 expressed in the peripheral nervous system are also reviewed. AQP4, the predominant water channel in the CNS, is involved both in the astrocyte swelling of cytotoxic edema and the resolution of vasogenic edema and is of pivotal importance in the pathology of brain disorders such as neuromyelitis optica, brain tumors, and neurodegenerative disorders. Moreover, AQP4 has been demonstrated as a functional regulator of recently discovered glymphatic system that is a main contributor to clearance of toxic macromolecule from the brain. Other AQPs are also involved in a variety of important physiological and pathological process in the brain. It has been suggested that AQPs could represent an important target in treatment of brain disorders like cerebral edema. Future investigations are necessary to elucidate the pathological significance of AQPs in the CNS.
Identifiants
pubmed: 36717489
doi: 10.1007/978-981-19-7415-1_7
doi:
Substances chimiques
Aquaporin 2
0
Aquaporins
0
Water
059QF0KO0R
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
99-124Informations de copyright
© 2023. The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.
Références
Badaut J, Fukuda AM, Jullienne A, Petry KG (2014) Aquaporin and brain diseases. Biochim Biophys Acta 1840(5):1554–1568
Agre P, King LS, Yasui M, Guggino WB, Ottersen OP, Fujiyoshi Y, Engel A, Nielsen S (2002) Aquaporin water channels – from atomic structure to clinical medicine. J Physiol 542(Pt 1):3–16
Syková E (2004) Extrasynaptic volume transmission and diffusion parameters of the extracellular space. Neuroscience 129(4):861–876
Kimelberg HK (2004) Water homeostasis in the brain: basic concepts. Neuroscience 129(4):851–860
Agre P, Nielsen S, Ottersen OP (2004) Towards a molecular understanding of water homeostasis in the brain. Neuroscience 129(4):849–850
Verkman AS, Anderson MO, Papadopoulos MC (2014) Aquaporins: important but elusive drug targets. Nat Rev Drug Discov 13(4):259–277
El Hindy N, Bankfalvi A, Herring A, Adamzik M, Lambertz N, Zhu Y, Siffert W, Sure U, Sandalcioglu IE (2013) Correlation of aquaporin-1 water channel protein expression with tumor angiogenesis in human astrocytoma. Anticancer Res 33(2):609–613
Preston GM, Carroll TP, Guggino WB, Agre P (1992) Appearance of water channels in Xenopus Oocytes expressing red-cell chip28 protein. Science 256(5055):385–387
Denker BM, Smith BL, Kuhajda FP, Agre P (1988) Identification, purification, and partial characterization of a novel Mr 28,000 integral membrane protein from erythrocytes and renal tubules. J Biol Chem 263(30):15634–15642
Maugeri R, Schiera G, Di Liegro CM, Fricano A, Iacopino DG, Di Liegro I (2016) Aquaporins and brain tumors. Int J Mol Sci 17(7):1029
Zador Z, Bloch O, Yao X, Manley GT (2007) Aquaporins: role in cerebral edema and brain water balance. Prog Brain Res 161:185–194
Wolburg H, Noell S, Fallier-Becker P, Mack AF, Wolburg-Buchholz K (2012) The disturbed blood–brain barrier in human glioblastoma. Mol Asp Med 33(5–6):579–589
Nielsen S, Smith BL, Christensen EI, Agre P (1993) Distribution of the aquaporin CHIP in secretory and resorptive epithelia and capillary endothelia. Proc Natl Acad Sci U S A 90(15):7275–7279
Saadoun S, Papadopoulos MC, Davies DC, Bell BA, Krishna S (2002) Increased aquaporin 1 water channel expression inhuman brain tumours. Brain J Cancer 87(6):621–623
Yamamoto N, Yoneda K, Asai K, Sobue K, Tada T, Fujita Y, Katsuya H, Fujita M, Aihara N, Mase M, Yamada K, Miura Y, Kato T (2001) Alterations in the expression of the AQP family in cultured rat astrocytes during hypoxia and reoxygenation. Mol Brain Res 90(1):26–38
Yang M, Gao F, Liu H, Yu WH, Sun SQ (2009) Temporal changes in expression of aquaporin3, -4, -5 and -8 in rat brains after permanent focal cerebral ischemia. Brain Res 1290:121–132
Jung JS, Bhat RV, Preston GM, Guggino WB, Baraban JM, Agre P (1994) Molecular characterization of an aquaporin cDNA from brain: candidate osmoreceptor and regulator of water balance. Proc Natl Acad Sci U S A 91(26):13052–13056
Nielsen S, Nagelhus EA, Amiry-Moghaddam M, Bourque C, Agre P, Ottersen OP (1997) Specialized membrane domains for water transport in glial cells: high-resolution immunogold cytochemistry of aquaporin–4 in rat brain. J Neurosci 17(1):171–180
Yamamoto N, Sobue K, Fujita M, Katsuya H, Asai K (2002) Differential regulation of aquaporin-5 and -9 expression in astrocytes by protein kinase A. Mol Brain Res 104(1):96–102
Nagase H, Ågren J, Saito A, Liu K, Agre P, Hazama A, Yasui M (2007) Molecular cloning and characterization of mouse aquaporin 6. Biochem Biophys Res Commun 352(1):12–16
Sakai H, Sato K, Kai Y, Shoji T, Hasegawa S, Nishizaki M, Sagara A, Yamashita A, Narita M (2014) Distribution of aquaporin genes and selection of individual reference genes for quantitative real-time RT-PCR analysis in multiple tissues of the mouse. Can J Physiol Pharmacol 92(9):789–796
Shin I, Kim HJ, Lee JE, Gye MC (2006) Aquaporin7 expression during perinatal development of mouse brain. Neurosci Lett 409(2):106–111
Li X, Lei T, Xia T, Chen X, Feng S, Chen H, Chen Z, Peng Y, Yang Z (2008) Molecular characterization, chromosomal and expression patterns of three aquaglyceroporins (AQP3, 7, 9) from pig. Comp Biochem Physiol B 149(3):468–476
Yaba A, Sozen B, Suzen B, Demir N (2017) Expression of aquaporin-7 and aquaporin-9 in tanycyte cells and choroid plexus during mouse estrus cycle. Morphologie 101(332):39–46
Zhu SJ, Wang KJ, Gan SW, Xu J, Xu SY, Sun SQ (2013) Expression of aquaporin8 in human astrocytomas: correlation with pathologic grade. Biochem Biophys Res Commun 440(1):168–172
Elkjaer M, Vajda Z, Nejsum LN, Kwon T, Jensen UB, Amiry-Moghaddam M, Frokiaer J, Nielsen S (2000) Immunolocalization of AQP9 in liver, epididymis, testis, spleen, and brain. Biochem Biophys Res Commun 276(3):1118–1128
Badaut J, Hirt L, Granziera C, Bogousslavsky J, Magistretti PJ, Regli L (2001) Astrocyte-specific expression of aquaporin-9 in mouse brain is increased after transient focal cerebral ischemia. J Cereb Blood Flow Metab 21(5):477–482
Gorelick DA, Praetorius J, Tsunenari T, Nielsen S, Agre P (2006) Aquaporin-11: a channel protein lacking apparent transport function expressed in brain. BMC Biochem 7:14
Koike S, Tanaka Y, Matsuzaki T, Morishita Y, Ishibashi K (2016) Aquaporin-11 (AQP11) expression in the mouse brain. Int J Mol Sci 17(6):861
Manley GT, Fujimura M, Ma T, Noshita N, Filiz F, Bollen AW, Chan P, Verkman A (2000) Aquaporin-4 deletion in mice reduces brain edema after acute water intoxication and ischemic stroke. Nat Med 6(2):159–163
Papadopoulos MC, Manley GT, Krishna S, Verkman A (2004) Aquaporin-4 facilitates reabsorption of excess fluid in vasogenic brain edema. FASEB J 18(11):1291–1293
Saadoun S, Papadopoulos MC, Hara-Chikuma M, Verkman AS (2005) Impairment of angiogenesis and cell migration by targeted aquaporin-1 gene disruption. Nature 434(7034):786–792
Lennon VA, Kryzer TJ, Pittock SJ, Verkman A, Hinson SR (2005) IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel. J Exp Med 202(4):473–477
Rasmussen MK, Mestre H, Nedergaard M (2018) The glymphatic pathway in neurological disorders. Lancet Neurol 17(11):1016–1024
Saadoun S, Papadopoulos MC, Watanabe H, Yan D, Manley GT, Verkman A (2005) Involvement of aquaporin-4 in astroglial cell migration and glial scar formation. J Cell Sci 118(Pt 24):5691–5698
Binder DK, Yao X, Zador Z, Sick TJ, Verkman AS, Manley GT (2006) Increased seizure duration and slowed potassium kinetics in mice lacking aquaporin-4 water channels. Glia 53(6):631–636
Oshio K, Watanabe H, Song Y, Verkman AS, Manley GT (2005) Reduced cerebrospinal fluid production and intracranial pressure in mice lacking choroid plexus water channel Aquaporin-1. FASEB J 19(1):76–78
Shields SD, Mazario J, Skinner K, Basbaum AI (2007) Anatomical and functional analysis of aquaporin 1, a water channel in primary afferent neurons. Pain 131(1–2):8–20
Oshio K, Watanabe H, Yan D, Verkman AS, Manley GT (2006) Impaired pain sensation in mice lacking Aquaporin-1 water channels. Biochem Biophys Res Commun 341(4):1022–1028
Fukuda AM, Pop V, Spagnoli D, Ashwal S, Obenaus A, Badaut J (2012) Delayed increase of astrocytic aquaporin 4 after juvenile traumatic brain injury: possible role in edema resolution? Neuroscience 222:366–378
Arciénega II, Brunet JF, Bloch J, Badaut J (2010) Cell locations for AQP1, AQP4 and 9 in the non-human primate brain. Neuroscience 167:1103–1114
Magni F, Chinello C, Raimondo F, Mocarelli P, Kienle MG, Pitto M (2008) AQP1 expression analysis in human diseases: implications for proteomic characterization. Expert Rev Proteomics 5(1):29–43
Endo M, Jain RK, Witwer B, Brown D (1999) Water channel (Aquaporin 1) expression and distribution in mammary carcinomas and glioblastomas. Microvasc Res 58(2):89–98
Johnson MD, O’Connell M (2013) Na-K-2Cl cotransporter and aquaporin 1 in arachnoid granulations, meningiomas, and meningiomas invading dura. Hum Pathol 44(6):1118–1124
Oshio K, Binder DK, Liang Y, Bollen A, Feuerstein B, Berger MS, Manley GT (2005) Expression of the aquaporin-1 water channel in human glial tumors. Neurosurgery 56(2):375–381
Hoshi A, Tsunoda A, Tada M, Nishizawa M, Ugawa Y, Kakita A (2017) Expression of aquaporin 1 and aquaporin 4 in the temporal neocortex of patients with parkinson's disease. Brain Pathol 27(2):160–168
Misawa T, Arima K, Mizusawa H, Satoh J (2008) Close association of water channel AQP1 with amyloid-beta deposition in Alzheimer disease brains. Acta Neuropathol 116(3):247–260
Ma T, Frigeri A, Hasegawa H, Verkman AS (1994) Cloning of a water channel homolog expressed in brain meningeal cells and kidney collecting duct that functions as a stilbene-sensitive glycerol transporter. J Biol Chem 269(34):21845–21849
Takata K, Matsuzaki T, Tajika Y (2004) Aquaporins: water channel proteins of the cell membrane. Prog Histochem Cytochem 39(1):1–83
Faragó N, Kocsis ÁK, Braskó C, Lovas S, Rózsa M, Baka J, Kovács B, Mikite K, Szemenyei V, Molnár G, Ozsvár A, Oláh G, Piszár I, Zvara Á, Patócs A, Barzó P, Puskás LG, Tamás G (2016) Human neuronal changes in brain edema and increased intracranial pressure. Acta Neuropathol Commun 4(1):78
Kunisawa K, Shimizu T, Kushima I, Aleksic B, Mori D, Osanai Y, Kobayashi K, Taylor AM, Bhat MA, Hayashi A, Baba H, Ozaki N, Ikenaka K (2018) Dysregulation of schizophrenia-related aquaporin 3 through disruption of paranode influences neuronal viability. J Neurochem 147(3):395–408
Bloch O, Manley GT (2007) The role of aquaporin-4 in cerebral water transport and edema. Neurosurg Focus 22(5):E3
Hubbard JA, Hsu MS, Seldin MM, Binder DK (2015) Expression of the astrocyte water channel aquaporin-4 in the mouse brain. ASN Neuro 7(5):1759091415605486
Oshio K, Binder DK, Yang B, Schecter S, Verkman AS, Manley GT (2004) Expression of aquaporin water channels in mouse spinal cord. Neuroscience 127(3):685–693
Nagelhus EA, Veruki ML, Torp R, Haug FM, Laake JH, Nielsen S, Agre P, Ottersen OP (1998) Aquaporin-4 water channel protein in the rat retina and optic nerve: polarized expression in Müller cells and fibrous astrocytes. J Neurosci 18(7):2506–2519
Venero J, Vizuete M, Ilundain A, Machado A, Echevarria M, Cano J (1999) Detailed localization of aquaporin-4 messenger RNA in the CNS: preferential expression in periventricular organs. Neuroscience 94(1):239–250
Badaut J, Nehlig A, Verbavatz JM, Stoeckel ME, Freund-Mercier MJ, Lasbennes F (2000) Hypervascularization in the magnocellular nuclei of the rat hypothalamus: relationship with the distribution of aquaporin-4 and markers of energy metabolism. J Neuroendocrinol 12(10):960–969
Hsu MS, Seldin M, Lee DJ, Seifert G, Steinhäuser C, Binder DK (2011) Laminar-specific and developmental expression of aquaporin-4 in the mouse hippocampus. Neuroscience 178:21–32
Papadopoulos MC, Verkman AS (2013) Aquaporin water channels in the nervous system. Nat Rev Neurosci 14(4):265–277
Nagelhus E, Mathiisen T, Ottersen O (2004) Aquaporin-4 in the central nervous system: cellular and subcellular distribution and coexpression with KIR4.1. Neuroscience 129(4):905–913
Hoshi A, Yamamoto T, Shimizu K, Ugawa Y, Nishizawa M, Takahashi H, Kakita A (2012) Characteristics of aquaporin expression surrounding senile plaques and cerebral amyloid angiopathy in Alzheimer disease. J Neuropathol Exp Neurol 71(8):750–759
Yang J, Lunde LK, Nuntagij P, Oguchi T, Camassa L, Nilsson LN, Lannfelt L, Xu Y, Amiry-Moghaddam M, Ottersen OP (2011) Loss of astrocyte polarization in the tg-ArcSwe mouse model of Alzheimer’s disease. J Alzheimers Dis 27(4):711–722
Moftakhar P, Lynch MD, Pomakian JL, Vinters HV (2010) Aquaporin expression in the brains of patients with or without cerebral amyloid angiopathy. J Neuropathol Exp Neurol 69(12):1201–1209
Kress BT, Iliff JJ, Xia M, Wang M, Wei H, Zeppenfeld D, Xie L, Kang H, Xu Q, Liew J, Plog BA, Ding F, Deane R, Nedergaard M (2014) Impairment of paravascular clearance pathways in the aging brain. Ann Neurol 76(6):845–861
Iliff JJ, Chen MJ, Plog BA, Zeppenfeld DM, Soltero M, Yang L, Singh I, Deane R, Nedergaard M (2014) Impairment of glymphatic pathway function promotes tau pathology after traumatic brain injury. J Neurosci 34(49):16180–16193
Hablitz LM, Plá V, Giannetto M, Vinitsky HS, Stæger FF, Metcalfe T, Nguyen R, Benrais A, Nedergaard M (2020) Circadian control of brain glymphatic and lymphatic fluid flow. Nat Commun 11(1):4411
Lananna BV, Nadarajah CJ, Izumo M, Cedeño MR, Xiong DD, Dimitry J, Tso CF, McKee CA, Griffin P, Sheehan PW, Haspel JA, Barres BA, Liddelow SA, Takahashi JS, Karatsoreos IN, Musiek ES (2018) Cell-autonomous regulation of astrocyte activation by the circadian clock protein BMAL1. Cell Rep 25(1):1–9.e8
Wu J, Carlock C, Shim J, Moreno-Gonzalez I, Glass W 2nd, Ross A, Barichello T, Quevedo J, Lou Y (2021) Requirement of brain interleukin33 for aquaporin4 expression in astrocytes and glymphatic drainage of abnormal tau. Mol Psychiatry 26(10):5912–5924
Smith AJ, Jin BJ, Ratelade J, Verkman AS (2014) Aggregation state determines the localization and function of M1–and M23–aquaporin-4 in astrocytes. J Cell Biol 204(4):559–573
Yang B, Brown D, Verkman A (1996) The mercurial insensitive water channel (AQP-4) forms orthogonal arrays in stably transfected Chinese hamster ovary cells. J Biol Chem 271(9):4577–4580
Furman CS, Gorelick-Feldman DA, Davidson KG, Yasumura T, Neely JD, Agre P, Rash JE (2003) Aquaporin-4 square array assembly: opposing actions of M1 and M23 isoforms. Proc Natl Acad Sci U S A 100(23):13609–13614
Nico B, Frigeri A, Nicchia GP, Quondamatteo F, Herken R, Errede M, Ribatti D, Svelto M, Roncali L (2001) Role of aquaporin-4 water channel in the development and integrity of the blood-brain barrier. J Cell Sci 114(Pt 7):1297–1307
Stokum JA, Gerzanich V, Simard JM (2016) Molecular pathophysiology of cerebral edema. J Cereb Blood Flow Metab 36(3):513–538
Potokar M, Jorgačevski J, Zorec R (2016) Astrocyte aquaporin dynamics in health and disease. Int J Mol Sci 17(7):1121
Yang M, Gao F, Liu H, Yu W, He G, Zhuo F, Qiu G, Sun S (2011) Immunolocalization of aquaporins in rat brain. Anat Histol Embryol 40(4):299–306
Chai RC, Jiang JH, Wong K, Yuen A, Jiang F, Gao K, Vatcher G, Yu H, Cheung A (2013) AQP5 is differentially regulated in astrocytes during metabolic and traumatic injuries. Glia 61(10):1748–1765
Dobbs LG, Gonzalez R, Matthay MA, Carter EP, Allen L, Verkman AS (1998) Highly water-permeable type I alveolar epithelial cells confer high water permeability between the airspace and vasculature in rat lung. Proc Natl Acad Sci U S A 95(6):2991–2996
Agre P (2006) The aquaporin water channels. Proc Am Thorac Soc 3(1):5–13
Sveinsdottir S, Gram M, Cinthio M, Sveinsdottir K, Mörgelin M, Ley D (2014) Altered expression of aquaporin 1 and 5 in the choroid plexus following preterm intraventricular hemorrhage. Dev Neurosci 36(6):542–551
Lambertz N, Hindy NE, Adler C, Rump K, Adamzik M, Keyvani K, Bankfalvi A, Siffert W, Erol Sandalcioglu I, Bachmann HS (2013) Expression of aquaporin 5 and the AQP5 polymorphism A (-1364) C in association with peritumoral brain edema in meningioma patients. J Neuro-Oncol 112(2):297–305
Jeremic A, Cho WJ, Jena BP (2005) Involvement of water channels in synaptic vesicle swelling. Exp Biol Med 230(9):674–680
Ishibashi K, Kuwahara M, Gu Y, Kageyama Y, Tohsaka A, Suzuki F, Marumo F, Sasaki S (1997) Cloning and functional expression of a new water channel abundantly expressed in the testis permeable to water, glycerol, and urea. J Biol Chem 272(33):20782–20786
Yang B, Song Y, Zhao D, Verkman AS (2005) Phenotype analysis of aquaporin-8 null mice. Am J Physiol Cell Physiol 288(5):1161–1170
Chow PH, Bowen J, Yool AJ (2020) Combined systematic review and transcriptomic analyses of mammalian aquaporin classes 1 to 10 as biomarkers and prognostic indicators in diverse cancers. Cancer 12(7):1911
Badaut J, Petit JM, Brunet JF, Magistretti PJ, Charriaut-Marlangue C, Regli L (2004) Distribution of Aquaporin 9 in the adult rat brain: Preferential expression in catecholaminergic neurons and in glial cells. Neuroscience 128(1):27–38
Amiry-Moghaddam M, Lindland H, Zelenin S, Roberg BA, Gundersen BB, Petersen P, Rinvik E, Torgner IA, Ottersen OP (2005) Brain mitochondria contain aquaporin water channels: evidence for the expression of a short AQP9 isoform in the inner mitochondrial membrane. FASEB J 19(11):1459–1467
Jelen S, Parm Ulhøi B, Larsen A, Frøkiær J, Nielsen S, Rützler M (2013) AQP9 expression in glioblastoma multiforme tumors is limited to a small population of astrocytic cells and CD15(+)/CalB(+) leukocytes. PLoS One 8(9):e75764
Rojek AM, Skowronski MT, Füchtbauer EM, Füchtbauer AC, Fenton RA, Agre P, Frøkiær J, Nielsen S (2007) Defective glycerol metabolism in aquaporin 9 (AQP9) knockout mice. Proc Natl Acad Sci U S A 104(9):3609–3614
Ishibashi K, Kuwahara M, Kageyama Y, Sasaki S, Suzuki M, Imai M (2000) Molecular cloning of a new aquaporin superfamily in mammals. In: Molecular biology and physiology of water and solute transport. Springer, Cham, pp 123–126
Morishita Y, Matsuzaki T, Hara-chikuma M, Andoo A, Shimono M, Matsuki A, Kobayashi K, Ikeda M, Yamamoto T, Verkman A, Kusano E, Ookawara S, Takata K, Sasaki S, Ishibashi K (2005) Disruption of aquaporin-11 produces polycystic kidneys following vacuolization of the proximal tubule. Mol Cell Biol 25(17):7770–7779
Ishibashi K, Tanaka Y, Morishita Y (2014) The role of mammalian superaquaporins inside the cell. BBA-Gen Subjects 1840(5):1507–1512
Koike S, Tanaka Y, Morishita Y, Ishibashi K (2021) Effects of osmolality on the expression of brain aquaporins in AQP11-null mice. Biochimie 188:2–6
Xi T, Jin F, Zhu Y, Wang J, Tang L, Wang Y, Liebeskind DS, Scalzo F, He Z (2018) miR-27a-3p protects against blood-brain barrier disruption and brain injury after intracerebral hemorrhage by targeting endothelial aquaporin-11. J Biol Chem 293(52):20041–20050
Rajnarayanan R, Varadharajan S, Isokpehi R, Cohly H (2009) Potential role of cation-aquaporin interactions in autism. In: Biomedical science & engineering conference, 2009 first annual ORNL 2009, pp 1–4
Matsumoto I, Nagamatsu N, Arai S, Emori Y, Abe K (2004) Identification of candidate genes involved in somatosensory functions of cranial sensory ganglia. Mol Brain Res 126(1):98–102
Zhang H, Verkman AS (2010) Aquaporin-1 tunes pain perception by interaction with Nav1. 8 Na+ channels in dorsal root ganglion neurons. J Biol Chem 285(8):5896–5906
Ma TH, Gao HW, Fang XD, Yang H (2011) Expression and function of aquaporins in peripheral nervous system. Acta Pharmacol Sin 32(6):711–715
Zhang H, Verkman A (2015) Aquaporin-1 water permeability as a novel determinant of axonal regeneration in dorsal root ganglion neurons. Exp Neurol 265:152–159
Gao J, Tan M, Gu M, Marshall C, Ding J, Hu G, Xiao M (2012) Cellular localization of aquaporin-1 in the human and mouse trigeminal systems. PLoS One 7(9):e46379
Gao H, He C, Fang X, Hou X, Feng X, Yang H, Zhao X, Ma T (2006) Localization of aquaporin-1 water channel in glial cells of the human peripheral nervous system. Glia 53(7):783–787
Nagahama M, Ma N, Semba R, Naruse S (2006) Aquaporin 1 immunoreactive enteric neurons in the rat ileum. Neurosci Lett 395(3):206–210
Ishihara E, Nagahama M, Naruse S, Semba R, Miura T, Usami M, Narita M (2008) Neuropathological alteration of aquaporin 1 immunoreactive enteric neurons in the streptozotocin-induced diabetic rats. Auton Neurosci 138(1–2):31–40
Rinwa P, Calvo-Enrique L, Zhang MD, Nyengaard JR, Karlsson P, Ernfors P (2021) Demise of nociceptive Schwann cells causes nerve retraction and pain hyperalgesia. Pain 162(6):1816–1827
Borsani E, Bernardi S, Albertini R, Rezzani R, Rodella LF (2009) Alterations of AQP2 expression in trigeminal ganglia in a murine inflammation model. Neurosci Lett 449(3):183–188
Buffoli B, Borsani E, Rezzani R, Rodella LF (2009) Chronic constriction injury induces aquaporin-2 expression in the dorsal root ganglia of rats. J Anat 215(5):498–505
Thi MM, Spray DC, Hanani M (2008) Aquaporin-4 water channels in enteric neurons. J Neurosci Res 86(2):448–456
Kato J, Takai Y, Hayashi MK, Kato Y, Tanaka M, Sohma Y, Abe Y, Yasui M (2014) Expression and localization of aquaporin-4 in sensory ganglia. Biochem Biophys Res Commun 451(4):562–567
Jiang L, Li J, Liu X, Burnstock G, Xiang Z (2014) Expression of aquaporin-4 water channels in the digestive tract of the guinea pig. J Mol Histol 45(2):229–241
Kitada M, Suzuki H, Ichihashi J, Inada R, Miyamoto K, Takahashi T, Mitsui Y, Fujihara K, Kusunoki S (2012) Acute combined central and peripheral demyelination showing anti-aquaporin 4 antibody positivity. Intern Med 51(17):2443–2447
Toru S, Soejima I, Katayama Y, Saito K, Yokote H (2020) A case of anti-AQP4 antibody-positive neuromyelitis optica spectrum disorder with MRI-proven lesions in lumbar nerve roots. Mult Scler Relat Disord 46:102557
Mizuno Y, Shinoda K, Watanabe M, Ogata H, Isobe N, Matsushita T, Yamasaki R, Tanaka K, Koike H, Katsuno M, Kira JI (2019) Intractable axonal neuropathy with multifocal peripheral nerve swelling in neuromyelitis optica spectrum disorders: a case report. Mult Scler Relat Disord 35:16–18
Chang VTW, Chang HM (2020) Review: recent advances in the understanding of the pathophysiology of neuromyelitis optica spectrum disorder. Neuropathol Appl Neurobiol 46(3):199–218
Verkman A, Binder DK, Bloch O, Auguste K, Papadopoulos MC (2006) Three distinct roles of aquaporin-4 in brain function revealed by knockout mice. BBA-Biomembranes 1758(8):1085–1093
Yao X, Hrabětová S, Nicholson C, Manley GT (2008) Aquaporin-4-deficient mice have increased extracellular space without tortuosity change. J Neurosci 28(21):5460–5464
Hirt L, Fukuda AM, Ambadipudi K, Rashid F, Binder D, Verkman A, Ashwal S, Obenaus A, Badaut J (2017) Improved long-term outcome after transient cerebral ischemia in aquaporin-4 knockout mice. J Cereb Blood Flow Metab 37(1):277–290
Yang C, Liu Z, Li H, Zhai F, Liu J, Bian J (2015) Aquaporin-4 knockdown ameliorates hypoxic-ischemic cerebral edema in newborn piglets. IUBMB Life 67(3):182–190
Pizzo ML, Schiera G, Di Liegro I, Di Liegro CM, Pál J, Czeiter E, Sulyok E, Dóczi T (2013) Aquaporin-4 distribution in control and stressed astrocytes in culture and in the cerebrospinal fluid of patients with traumatic brain injuries. Neurol Sci 34(8):1309–1314
Yao X, Uchida K, Papadopoulos MC, Zador Z, Manley GT, Verkman AS (2015) Mildly reduced brain swelling and improved neurological outcome in aquaporin-4 knockout mice following controlled cortical impact brain injury. J Neurotrauma 32(19):1458–1464
Yao X, Derugin N, Manley GT, Verkman AS (2015) Reduced brain edema and infarct volume in aquaporin-4 deficient mice after transient focal cerebral ischemia. Neurosci Lett 584:368–372
Saadoun S, Bell BA, Verkman A, Papadopoulos MC (2008) Greatly improved neurological outcome after spinal cord compression injury in AQP4-deficient mice. Brain 131(Pt 4):1087–1098
Kimura A, Hsu M, Seldin M, Verkman AS, Scharfman HE, Binder DK (2010) Protective role of aquaporin-4 water channels after contusion spinal cord injury. Ann Neurol 67(6):794–801
Mou K, Chen M, Mao Q, Wang P, Ni R, Xia X, Liu Y (2010) AQP-4 in peritumoral edematous tissue is correlated with the degree of glioma and with expression of VEGF and HIF-alpha. J Neuro-Oncol 100(3):375–383
Papadopoulos MC, Verkman A (2005) Aquaporin-4 gene disruption in mice reduces brain swelling and mortality in pneumococcal meningitis. J Biol Chem 280(14):13906–13912
Amiry-Moghaddam M, Xue R, Haug FM, Neely JD, Bhardwaj A, Agre P, Adams ME, Froehner SC, Mori S, Ottersen OP (2004) Alpha-syntrophin deletion removes the perivascular but not endothelial pool of aquaporin-4 at the blood-brain barrier and delays the development of brain edema in an experimental model of acute hyponatremia. FASEB J 18(3):542–544
Yang B, Zador Z, Verkman AS (2008) Glial cell aquaporin-4 overexpression in transgenic mice accelerates cytotoxic brain swelling. J Biol Chem 283(22):15280–15286
Amiry-Moghaddam M, Ottersen OP (2003) The molecular basis of water transport in the brain. Nat Rev Neurosci 4(12):991–1001
Bloch O, Auguste KI, Manley GT, Verkman A (2006) Accelerated progression of kaolin-induced hydrocephalus in aquaporin-4-deficient mice. J Cereb Blood Flow Metab 26(12):1527–1537
Zhou J, Kong H, Hua X, Xiao M, Ding J, Hu G (2008) Altered blood–brain barrier integrity in adult aquaporin-4 knockout mice. Neuroreport 19(1):1–5
Wu Q, Zhang YJ, Gao JY, Li XM, Kong H, Zhang YP, Xiao M, Shields CB, Hu G (2014) Aquaporin-4 mitigates retrograde degeneration of rubrospinal neurons by facilitating edema clearance and glial scar formation after spinal cord injury in mice. Mol Neurobiol 49(3):1327–1337
Juenemann M, Braun T, Doenges S, Nedelmann M, Mueller C, Bachmann G, Singh P, Blaes F, Gerriets T, Tschernatsch M (2015) Aquaporin-4 autoantibodies increase vasogenic edema formation and infarct size in a rat stroke model. BMC Immunol 16:3
Vella J, Zammit C, Di Giovanni G, Muscat R, Valentino M (2015) The central role of aquaporins in the pathophysiology of ischemic stroke. Front Cell Neurosci 9:108
Bloch O, Papadopoulos MC, Manley GT, Verkman AS (2005) Aquaporin-4 gene deletion in mice increases focal edema associated with staphylococcal brain abscess. J Neurochem 95(1):254–262
Nagelhus EA, Ottersen OP (2013) Physiological roles of aquaporin-4 in brain. Physiol Rev 93(4):1543–1562
Wen H, Nagelhus EA, Amiry-Moghaddam M, Agre P, Ottersen OP, Nielsen S (1999) Ontogeny of water transport in rat brain: postnatal expression of the aquaporin-4 water channel. Eur J Neurosci 11(3):935–945
Nico B, Paola Nicchia G, Frigeri A, Corsi P, Mangieri D, Ribatti D, Svelto M, Roncali L (2004) Altered blood–brain barrier development in dystrophic MDX mice. Neuroscience 125(4):921–935
Nicchia GP, Nico B, Camassa LMA, Mola MG, Loh N, Dermietzel R, Spray DC, Svelto M, Frigeri A (2004) The role of aquaporin-4 in the blood–brain barrier development and integrity: Studies in animal and cell culture models. Neuroscience 129(4):935–945
Li X, Gao J, Ding J, Hu G, Xiao M (2013) Aquaporin-4 expression contributes to decreases in brain water content during mouse postnatal development. Brain Res Bull 94:49–55
Haj-Yasein NN, Vindedal GF, Eilert-Olsen M, Gundersen GA, Skare Ø, Laake P, Klungland A, Thorén AE, Burkhardt JM, Ottersen OP, Nagelhus EA (2011) Glial-conditional deletion of aquaporin-4 (Aqp4) reduces blood–brain water uptake and confers barrier function on perivascular astrocyte endfeet. Proc Natl Acad Sci U S A 108(43):17815–17820
Tarasoff-Conway JM, Carare RO, Osorio RS, Glodzik L, Butler T, Fieremans E, Axel L, Rusinek H, Nicholson C, Zlokovic BV, Frangione B, Blennow K, Ménard J, Zetterberg H, Wisniewski T, de Leon MJ (2015) Clearance systems in the brain—implications for Alzheimer disease. Nat Rev Neurol 11(8):457–470
Iliff JJ, Wang M, Liao Y, Plogg BA, Peng W, Gundersen GA, Benveniste H, Vates GE, Deane R, Goldman SA, Nagelhus EA, Nedergaard M (2012) A Paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β. Sci Transl Med 4:147
Zou W, Pu T, Feng W, Lu M, Zheng Y, Du R, Xiao M, Hu G (2019) Blocking meningeal lymphatic drainage aggravates Parkinson's disease-like pathology in mice overexpressing mutated α-synuclein. Transl Neurodegener 8:7
Iliff JJ, Goldman SA, Nedergaard M (2015) Implications of the discovery of brain lymphatic pathways. Lancet Neurol 14(10):977–979
Louveau A, Smirnov I, Keyes TJ, Eccles JD, Rouhani SJ, Peske JD, Derecki NC, Castle D, Mandell JW, Kevin SL, Harris TH, Kipnis J (2015) Structural and functional features of central nervous system lymphatics. Nature 523(7560):337–341
Eide PK, Ringstad G (2015) MRI with intrathecal MRI gadolinium contrast medium administration: a possible method to assess glymphatic function in human brain. Acta Radiol Open 4(11):2058460115609635
Aspelund A, Antila S, Proulx ST, Karlsen TV, Karaman S, Detmar M, Wiig H, Alitalo K (2015) A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules. J Exp Med 212(7):991–999
Morris AWJ, Sharp MM, Albargothy NJ, Fernandes R, Hawkes CA, Verma A, Weller RO, Carare RO (2016) Vascular basement membranes as pathways for the passage of fluid into and out of the brain. Acta Neuropathol 131(5):725–736
Cserr HF, Harling-Berg CJ, Knopf PM (1992) Drainage of brain extracellular fluid into blood and deep cervical lymph and its immunological significance. Brain Pathol 2(4):269–276
Peng W, Achariyar TM, Li B, Liao Y, Mestre H, Hitomi E, Regan S, Kasper T, Peng S, Ding F, Benveniste H, Nedergaard M, Deane R (2016) Suppression of glymphatic fluid transport in a mouse model of Alzheimer’s disease. Neurobiol Dis 93:215–225
He XF, Liu DX, Zhang Q, Liang FY, Dai GY, Zeng JS, Pei Z, Xu GQ, Lan Y (2017) Voluntary exercise promotes glymphatic clearance of amyloid beta and reduces the cctivation of astrocytes and microglia in aged mice. Front Mol Neurosci 10:144
Liu Y, Hu PP, Zhai S, Feng WX, Zhang R, Li Q, Marshall C, Xiao M, Wu T (2022) Aquaporin 4 deficiency eliminates the beneficial effects of voluntary exercise in a mouse model of Alzheimer’s disease. Neural Regen Res 17(9):2079–2088
Butt AM, Kalsi A (2006) Inwardly rectifying potassium channels (Kir) in central nervous system glia: a special role for Kir4.1 in glial functions. J Cell Mol Med 10(1):33–44
Nagelhus EA, Horio Y, Inanobe A, Fujita A, Fm H, Nielsen S, Kurachi Y, Ottersen OP (1999) Immunogold evidence suggests that coupling of K+ siphoning and water transport in rat retinal Müller cells is mediated by a coenrichment of Kir4.1 and AQP4 in specific membrane domains. Glia 26(1):47–54
Ruiz-Ederra J, Zhang H, Verkman AS (2007) Evidence against functional interaction between aquaporin-4 water channels and Kir4.1 potassium channels in retinal Müller cells. J Biol Chem 282(30):21866–21872
Amiry-Moghaddam M, Williamson A, Palomba M, Eid T, de Lanerolle NC, Nagelhus EA, Adams ME, Froehner SC, Agre P, Ottersen OP (2003) Delayed K+ clearance associated with aquaporin-4 mislocalization: phenotypic defects in brains of α-syntrophin-null mice. Proc Natl Acad Sci U S A 100(23):13615–13620
Strohschein S, Hüttmann K, Gabriel S, Binder DK, Heinemann U, Steinhäuser C (2011) Impact of aquaporin-4 channels on K+ buffering and gap junction coupling in the hippocampus. Glia 59(6):973–980
Haj-Yasein NN, Bugge CE, Jensen V, Østby I, Ottersen OP, Hvalby Ø, Nagelhus EA (2015) Deletion of aquaporin-4 increases extracellular K(+) concentration during synaptic stimulation in mouse hippocampus. Brain Struct Funct 220(4):2469–2474
Dietzel I, Heinemann U, Hofmeier G, Lux H (1980) Transient changes in the size of the extracellular space in the sensorimotor cortex of cats in relation to stimulus-induced changes in potassium concentration. Exp Brain Res 40(4):432–439
Syková E, Chvátal A (2000) Glial cells and volume transmission in the CNS. Neurochem Int 36(4–5):397–409
Jayakumar AR, Rao KVR, Tong XY, Norenberg MD (2009) Calcium in the mechanism of ammonia-induced astrocyte swelling. J Neurochem 109(1):252–257
Thrane AS, Rappold PM, Fujita T, Torres A, Bekar LK, Takano T, Peng W, Wang F, Thrane VR, Enger R (2011) Critical role of aquaporin-4 (AQP4) in astrocytic Ca2+ signaling events elicited by cerebral edema. Proc Natl Acad Sci U S A 108(2):846–851
Benfenati V, Caprini M, Dovizio M, Mylonakou MN, Ferroni S, Ottersen OP, Amiry-Moghaddam M (2011) An aquaporin-4/transient receptor potential vanilloid 4 (AQP4/TRPV4) complex is essential for cell-volume control in astrocytes. Proc Natl Acad Sci U S A 108(6):2563–2568
Jo AO, Ryskamp DA, Phuong TTT, Verkman AS, Yarishkin O, MacAulay N, Križaj D (2015) TRPV4 and AQP4 channels synergistically regulate cell volume and calcium homeostasis in retinal müller glia. J Neurosci 35(39):13525–13537
O’Shea R (2002) Roles and regulation of glutamate transporters in the central nervous system. Clin Exp Pharmacol Physiol 29(11):1018–1023
Gunnarson E, Zelenina M, Axehult G, Song Y, Bondar A, Krieger P, Brismar H, Zelenin S, Aperia A (2008) Identification of a molecular target for glutamate regulation of astrocyte water permeability. Glia 56(6):587–596
Li YK, Wang F, Wang W, Luo Y, Wu PF, Xiao JL, Hu ZL, Jin Y, Hu G, Chen JG (2012) Aquaporin-4 deficiency impairs synaptic plasticity and associative fear memory in the lateral amygdala: involvement of downregulation of glutamate transporter-1 expression. Neuropsychopharmacology 37(8):1867–1878
Zeng XN, Sun XL, Gao L, Fan Y, Ding JH, Hu G (2007) Aquaporin-4 deficiency down-regulates glutamate uptake and GLT-1 expression in astrocytes. Mol Cell Neurosci 34(1):34–39
Wu N, Lu XQ, Yan HT, Su RB, Wang J-F, Liu Y, Hu G, Li J (2008) Aquaporin 4 deficiency modulates morphine pharmacological actions. Neurosci Lett 448(2):221–225
Yan HT, Wu N, Lu XQ, Su RB, Zheng JQ, Li J (2013) Aquaporin-4 deficiency attenuates opioid dependence through suppressing glutamate transporter-1 down-regulation and maintaining glutamate homeostasis. CNS Neurosci Ther 19(1):12–19
Fan Y, Zhang J, Sun XL, Gao L, Zeng XN, Ding JH, Cao C, Niu L, Hu G (2005) Sex-and region-specific alterations of basal amino acid and monoamine metabolism in the brain of aquaporin-4 knockout mice. J Neurosci Res 82(4):458–464
Ding JH, Sha LL, Chang J, Zhou XQ, Fan Y, Hu G (2007) Alterations of striatal neurotransmitter release in aquaporin-4 deficient mice: an in vivo microdialysis study. Neurosci Lett 422(3):175–180
Filosa A, Paixão S, Honsek SD, Carmona MA, Becker L, Feddersen B, Gaitanos L, Rudhard Y, Schoepfer R, Klopstock T (2009) Neuron-glia communication via EphA4/ephrin-A3 modulates LTP through glial glutamate transport. Nat Neurosci 12(10):1285–1292
Haydon PG, Blendy J, Moss SJ, Jackson FR (2009) Astrocytic control of synaptic transmission and plasticity: a target for drugs of abuse? Neuropharmacology 56(Suppl 1):83–90
Perea G, Navarrete M, Araque A (2009) Tripartite synapses: astrocytes process and control synaptic information. Trends Neurosci 32(8):421–431
Szu JI, Binder DK (2016) The role of astrocytic aquaporin-4 in synaptic plasticity and learning and memory. Front Integr Neurosci 10:8
Scharfman HE, Binder DK (2013) Aquaporin-4 water channels and synaptic plasticity in the hippocampus. Neurochem Int 63(7):702–711
Skucas VA, Mathews IB, Yang J, Cheng Q, Treister A, Duffy AM, Verkman AS, Hempstead BL, Wood MA, Binder DK (2011) Impairment of select forms of spatial memory and neurotrophin-dependent synaptic plasticity by deletion of glial aquaporin-4. J Neurosci 31(17):6392–6397
Kong H, Sha LL, Fan Y, Xiao M, Ding JH, Wu J, Hu G (2009) Requirement of AQP4 for antidepressive efficiency of fluoxetine: implication in adult hippocampal neurogenesis. Neuropsychopharmacology 34(5):1263–1276
Lussier AL, Lebedeva K, Fenton EY, Guskjolen A, Caruncho HJ, Kalynchuk LE (2013) The progressive development of depression-like behavior in corticosterone-treated rats is paralleled by slowed granule cell maturation and decreased reelin expression in the adult dentate gyrus. Neuropharmacology 71:174–183
Snyder JS, Soumier A, Brewer M, Pickel J, Cameron HA (2011) Adult hippocampal neurogenesis buffers stress responses and depressive behaviour. Nature 476(7361):458–461
Kong H, Fan Y, Xie J, Ding J, Sha L, Shi X, Sun X, Hu G (2008) AQP4 knockout impairs proliferation, migration and neuronal differentiation of adult neural stem cells. J Cell Sci 121(Pt 24):4029–4036
Kong H, Zeng XN, Fan Y, Yuan ST, Ge S, Xie WP, Wang H, Hu G (2014) Aquaporin-4 knockout exacerbates corticosterone-induced depression by inhibiting astrocyte function and hippocampal neurogenesis. CNS Neurosci Ther 20(5):391–402
Basco D, Nicchia GP, D'Alessandro A, Zolla L, Svelto M, Frigeri A (2011) Absence of aquaporin-4 in skeletal muscle alters proteins involved in bioenergetic pathways and calcium handling. PLoS One 6(4):e19225
Cheng YS, Tang YQ, Dai DZ, Dai Y (2012) AQP4 knockout mice manifest abnormal expressions of calcium handling proteins possibly due to exacerbating pro-inflammatory factors in the heart. Biochem Pharmacol 83(1):97–105
Fossdal G, Vik-Mo EO, Sandberg C, Varghese M, Kaarbø M, Telmo E, Langmoen IA, Murrell W (2012) Aqp 9 and brain tumour stem cells. Sci World J 2012:915176
Badaut J, Brunet JF, Petit JM, Guérin CF, Magistretti PJ, Regli L (2008) Induction of brain aquaporin 9 (AQP9) in catecholaminergic neurons in diabetic rats. Brain Res 1188:17–24
Tan G, Sun S, Yuan D (2008) Expression of the water channel protein aquaporin-9 in human astrocytic tumours: correlation with pathological grade. J Int Med Res 36(4):777–782
Wei X, Ren X, Jiang R, Li H, Gao F, Chen Y, Hou J, Liu X, Sun S, Yang M (2015) Phosphorylation of p38 MAPK mediates aquaporin 9 expression in rat brains during permanent focal cerebral ischaemia. J Mol Histol 46(3):273–281
Sun Z, Zhao Z, Zhao S, Sheng Y, Zhao Z, Gao C, Li J, Liu X (2008) Recombinant hirudin treatment modulates aquaporin-4 and aquaporin-9 expression after intracerebral hemorrhage in vivo. Mol Biol Rep 36(5):1119–1127
Ji W, Wang J, Xu J, Zhao X, Xu X, Lu X (2017) Lack of aquaporin 9 reduces brain angiogenesis and exaggerates neuronal loss in the hippocampus following intracranial hemorrhage in mice. J Mol Neurosci 61(3):351–358
Auguste KI, Jin S, Uchida K, Yan D, Manley GT, Papadopoulos MC, Verkman A (2007) Greatly impaired migration of implanted aquaporin-4-deficient astroglial cells in mouse brain toward a site of injury. FASEB J 21(1):108–116
Musa-Aziz R, Chen LM, Pelletier MF, Boron WF, Giebisch G (2009) Relative CO
Hiroaki Y, Tani K, Kamegawa A, Gyobu N, Nishikawa K, Suzuki H, Walz T, Sasaki S, Mitsuoka K, Kimura K (2006) Implications of the aquaporin-4 structure on array formation and cell adhesion. J Mol Biol 355(4):628–639
Assentoft M, Larsen BR, MacAulay N (2015) Regulation and function of AQP4 in the central nervous system. Neurochem Res 40(12):2615–2627
Ximenes-Da-Silva A (2016) Metal ion toxins and brain aquaporin-4 expression: an overview. Front Neurosci 10:233
Iuso A, Križaj D (2016) TRPV4-AQP4 interactions ‘turbocharge’ astroglial sensitivity to small osmotic gradients. Channels 10(3):172–174
Warth A, Simon P, Capper D, Goeppert B, Tabatabai G, Herzog H, Dietz K, Stubenvoll F, Ajaaj R, Becker R (2007) Expression pattern of the water channel aquaporin-4 in human gliomas is associated with blood–brain barrier disturbance but not with patient survival. J Neurosci Res 85(6):1336–1346
Saadoun S, Papadopoulos M, Davies D, Krishna S, Bell B (2002) Aquaporin-4 expression is increased in oedematous human brain tumours. J Neurol Neurosurg Psychiatry 72(2):262–265
De Castro RM, Hirt L, Bogousslavsky J, Regli L, Badaut J (2006) Time course of aquaporin expression after transient focal cerebral ischemia in mice. J Neurosci Res 83(7):1231–1240
Hirt L, Price M, Ternon B, Mastour N, Brunet J, Badaut J (2009) Early induction of AQP4 contributes the limitation of the edema formation in the brain ischemia. J Cereb Blood Flow Metab 29(2):423–433
Ding JY, Kreipke CW, Speirs SL, Schafer P, Schafer S, Rafols JA (2009) Hypoxia-inducible factor-1α signaling in aquaporin upregulation after traumatic brain injury. Neurosci Lett 453(1):68–72
Sun MC, Honey CR, Berk C, Wong NL, Tsui JK (2003) Regulation of aquaporin-4 in a traumatic brain injury model in rats. J Neurosurg 98(3):565–569
Tourdias T, Mori N, Dragonu I, Cassagno N, Boiziau C, Aussudre J, Brochet B, Moonen C, Petry KG, Dousset V (2011) Differential aquaporin 4 expression during edema build-up and resolution phases of brain inflammation. J Neuroinflammation 8:143
Tourdias T, Dragonu I, Fushimi Y, Deloire MS, Boiziau C, Brochet B, Moonen C, Petry KG, Dousset V (2009) Aquaporin 4 correlates with apparent diffusion coefficient and hydrocephalus severity in the rat brain: a combined MRI–histological study. NeuroImage 47(2):659–666
Ke C, Poon WS, Ng HK, Pang JC, Chan Y (2001) Heterogeneous responses of aquaporin-4 in oedema formation in a replicated severe traumatic brain injury model in rats. Neurosci Lett 301(1):21–24
Kiening KL, van Landeghem FK, Schreiber S, Thomale UW, von Deimling A, Unterberg AW, Stover JF (2002) Decreased hemispheric aquaporin-4 is linked to evolving brain edema following controlled cortical impact injury in rats. Neurosci Lett 324(2):105–108
Hubbard JA, Szu JI, Yonan JM, Binder DK (2016) Regulation of astrocyte glutamate transporter-1 (GLT1) and aquaporin-4 (AQP4) expression in a model of epilepsy. Exp Neurol 283(Pt A):85–96
Genel O, Pariante CM, Borsini A (2021) The role of AQP4 in the pathogenesis of depression, and possible related mechanisms. Brain Behav Immun 98:366–377
Wilcock DM, Vitek MP, Colton CA (2009) Vascular amyloid alters astrocytic water and potassium channels in mouse models and humans with Alzheimer’s disease. Neuroscience 159(3):1055–1069
Badaut J, Ashwal S, Obenaus A (2011) Aquaporins in cerebrovascular disease: a target for treatment of brain edema. Cerebrovasc Dis 31(16):521–531
Simard JM, Kent TA, Chen M, Tarasov KV, Gerzanich V (2007) Brain oedema in focal ischaemia: molecular pathophysiology and theoretical implications. Lancet Neurol 6(3):258–268
Ren Z, Iliff JJ, Yang L, Yang J, Chen X, Chen MJ, Giese RN, Wang B, Shi X, Nedergaard M (2013) ‘Hit & Run’ model of closed-skull traumatic brain injury (TBI) reveals complex patterns of post-traumatic AQP4 dysregulation. J Cereb Blood Flow Metab 33(6):834–845
Steiner E, Enzmann GU, Lin S, Ghavampour S, Hannocks MJ, Zuber B, Rüegg MA, Sorokin L, Engelhardt B (2012) Loss of astrocyte polarization upon transient focal brain ischemia as a possible mechanism to counteract early edema formation. Glia 60(11):1646–1659
Stokum JA, Kurland DB, Gerzanich V, Simard JM (2015) Mechanisms of astrocyte-mediated cerebral edema. Neurochem Res 40(2):317–328
Badaut J, Ashwal S, Adami A, Tone B, Recker R, Spagnoli D, Ternon B, Obenaus A (2011) Brain water mobility decreases after astrocytic aquaporin-4 inhibition using RNA interference. J Cereb Blood Flow Metab 31(3):819–831
Fukuda AM, Adami A, Pop V, Bellone JA, Coats JS, Hartman RE, Ashwal S, Obenaus A, Badaut J (2013) Posttraumatic reduction of edema with aquaporin-4 RNA interference improves acute and chronic functional recovery. J Cereb Blood Flow Metab 33(10):1621–1632
Smith AJ, Jin BJ, Verkman AS (2015) Muddying the water in brain edema? Trends Neurosci 38(6):331–332
Mestre H, Du T, Sweeney AM, Liu G, Samson AJ, Peng W, Mortensen KN, Stæger FF, Bork PAR, Bashford L, Toro ER, Tithof J, Kelley DH, Thomas JH, Hjorth PG, Martens EA, Mehta RI, Solis O, Blinder P, Kleinfeld D, Hirase H, Mori Y, Nedergaard M (2020) Cerebrospinal fluid influx drives acute ischemic tissue swelling. Science 367(6483):7171
Marignier R, Giraudon P, Vukusic S, Confavreux C, Honnorat J (2010) Anti-aquaporin-4 antibodies in Devic’s neuromyelitis optica: therapeutic implications. Ther Adv Neurol Disord 3(5):311–321
Mangiatordi GF, Alberga D, Trisciuzzi D, Lattanzi G, Nicolotti O (2016) Human aquaporin-4 and molecular modeling: historical perspective and view to the future. Int J Mol Sci 17(7):1119
Papadopoulos MC, Verkman AS (2012) Aquaporin 4 and neuromyelitis optica. Lancet Neurol 11(6):535–544
Yang X, Ransom BR, Ma JF (2016) The role of AQP4 in neuromyelitis optica: more answers, more questions. J Neuroimmunol 298:63–70
Hinson SR, Romero MF, Popescu BFG, Lucchinetti CF, Fryer JP, Wolburg H, Fallier-Becker P, Noell S, Lennon VA (2012) Molecular outcomes of neuromyelitis optica (NMO)-IgG binding to aquaporin-4 in astrocytes. Proc Natl Acad Sci U S A 109(4):1245–1250
Crane JM, Lam C, Rossi A, Gupta T, Bennett JL, Verkman A (2011) Binding affinity and specificity of neuromyelitis optica autoantibodies to aquaporin-4 M1/M23 isoforms and orthogonal arrays. J Biol Chem 286(18):16516–16524
Phuan PW, Ratelade J, Rossi A, Tradtrantip L, Verkman AS (2012) Complement-dependent cytotoxicity in neuromyelitis optica requires aquaporin-4 protein assembly in orthogonal arrays. J Biol Chem 287(17):13829–13839
Rossi A, Ratelade J, Papadopoulos MC, Bennett JL, Verkman A (2012) Neuromyelitis optica IgG does not alter aquaporin-4 water permeability, plasma membrane M1/M23 isoform content, or supramolecular assembly. Glia 60(12):2027–2039
Tradtrantip L, Zhang H, Saadoun S, Phuan PW, Lam C, Papadopoulos MC, Bennett JL, Verkman AS (2012) Anti–aquaporin-4 monoclonal antibody blocker therapy for neuromyelitis optica. Ann Neurol 71(3):314–322
Tradtrantip L, Zhang H, Anderson MO, Saadoun S, Phuan PW, Papadopoulos MC, Bennett JL, Verkman A (2012) Small-molecule inhibitors of NMO-IgG binding to aquaporin-4 reduce astrocyte cytotoxicity in neuromyelitis optica. FASEB J 26(5):2197–2208
Tradtrantip L, Ratelade J, Zhang H, Verkman A (2013) Enzymatic deglycosylation converts pathogenic neuromyelitis optica anti-aquaporin-4 immunoglobulin G into therapeutic antibody. Ann Neurol 73(1):77–88
Tradtrantip L, Asavapanumas N, Verkman AS (2013) Therapeutic cleavage of anti–aquaporin-4 autoantibody in neuromyelitis optica by an IgG-selective proteinase. Mol Pharmacol 83(6):1268–1278
Son M, Kim D, Park KS, Hong S, Park TH (2016) Detection of aquaporin-4 antibody using aquaporin-4 extracellular loop-based carbon nanotube biosensor for the diagnosis of neuromyelitis optica. Biosens Bioelectron 78:87–91
Pittock SJ (2016) Demyelinating disease. NMO spectrum disorders: clinical or molecular classification? Nat Rev Neurol 12(3):129–130
Brill L, Mandel M, Karussis D, Petrou P, Miller K, Ben-Hur T, Karni A, Paltiel O, Israel S, Vaknin-Dembinsky A (2016) Increased occurrence of anti-AQP4 seropositivity and unique HLA Class II associations with neuromyelitis optica (NMO), among Muslim Arabs in Israel. J Neuroimmunol 293:65–70
Markert JM, Fuller CM, Gillespie GY, Bubien JK, Mclean LA, Hong RL, Lee K, Gullans SR, Mapstone TB, Benos DJ (2001) Differential gene expression profiling in human brain tumors. Physiol Genomics 5(1):21–33
Boon K, Edwards JB, Eberhart CG, Riggins GJ (2004) Identification of astrocytoma associated genes including cell surface markers. BMC Cancer 4:39
El Hindy N, Rump K, Lambertz N, Zhu Y, Frey UH, Bankfalvi A, Siffert W, Sure U, Peters J, Adamzik M, Sandalcioglu IE (2013) The functional aquaporin 1-783G/C-polymorphism is associated with survival in patients with glioblastoma multiforme. J Surg Oncol 108(7):492–498
Stroka Kimberly M, Jiang H, Chen SH, Tong Z, Wirtz D, Sun Sean X, Konstantopoulos K (2014) Water permeation drives tumor cell migration in confined microenvironments. Cell 157(3):611–623
Papadopoulos MC, Saadoun S (2015) Key roles of aquaporins in tumor biology. BBA-Biomembranes 1848(10):2576–2583
Longatti P, Basaldella L, Orvieto E, Dei Tos A, Martinuzzi A (2006) Aquaporin (s) expression in choroid plexus tumours. Pediatr Neurosurg 42(4):228–233
Noell S, Fallier-Becker P, Mack AF, Hoffmeister M, Beschorner R, Ritz R (2015) Water channels aquaporin 4 and-1 expression in subependymoma depends on the localization of the tumors. PLoS One 10(6):e0131367
Satoh J, Tabunoki H, Yamamura T, Arima K, Konno H (2007) Human astrocytes express aquaporin-1 and aquaporin-4 in vitro and in vivo. Neuropathology 27(3):245–256
McCoy E, Sontheimer H (2007) Expression and function of water channels (aquaporins) in migrating malignant astrocytes. Glia 55(10):1034–1043
Ding T, Gu F, Fu L, Ma YJ (2010) Aquaporin-4 in glioma invasion and an analysis of molecular mechanisms. J Clin Neurosci 17(11):1359–1361
Ding T, Ma Y, Li W, Liu X, Ying G, Fu L, Gu F (2011) Role of aquaporin-4 in the regulation of migration and invasion of human glioma cells. Int J Oncol 38(6):1521–1531
Ding T, Zhou Y, Sun K, Jiang W, Li W, Liu X, Tian C, Li Z, Ying G, Fu L (2013) Knockdown a water channel protein, aquaporin-4, induced glioblastoma cell apoptosis. PLoS One 8(8):e66751
Zhang H, Verkman AS (2008) Evidence against involvement of aquaporin-4 in cell–cell adhesion. J Mol Biol 382(5):1136–1143
Goedert M, Spillantini MG (2006) A century of Alzheimer’s disease. Science 314(5800):777–781
Pérez E, Barrachina M, Rodríguez A, Torrejón-Escribano B, Boada M, Hernández I, Sánchez M, Ferrer I (2007) Aquaporin expression in the cerebral cortex is increased at early stages of Alzheimer disease. Brain Res 1128(1):164–174
Huysseune S, Kienlen-Campard P, Hébert S, Tasiaux B, Leroy K, Devuyst O, Brion JP, De Strooper B, Octave JN (2009) Epigenetic control of aquaporin 1 expression by the amyloid precursor protein. FASEB J 23(12):4158–4167
Sadashima S, Honda H, Suzuki SO, Shijo M, Aishima S, Kai K, Kira J, Iwaki T (2020) Accumulation of astrocytic aquaporin 4 and aquaporin 1 in prion protein plaques. J Neuropathol Exp Neurol 79:419–429
Rodríguez A, Pérez-Gracia E, Espinosa JC, Pumarola M, Torres JM, Ferrer I (2006) Increased expression of water channel aquaporin 1 and aquaporin 4 in Creutzfeldt-Jakob disease and in bovine spongiform encephalopathy-infected bovine-PrP transgenic mice. Acta Neuropathol 112(5):573–585
Yu B, Zhang J, Li H, Sun X (2020) Silencing of aquaporin1 activates the Wnt signaling pathway to improve cognitive function in a mouse model of Alzheimer’s disease. Gene 755:144904
González-Marrero I, Giménez-Llort L, Johanson CE, Carmona-Calero EM, Castañeyra-Ruiz L, Brito-Armas JM, Castañeyra-Perdomo A, Castro-Fuentes R (2015) Choroid plexus dysfunction impairs beta-amyloid clearance in a triple transgenic mouse model of Alzheimer’s disease. Front Cell Neurosci 9:17
Shin J, Yu SB, Yu UY, Jo SA, Ahn JH (2010) Swedish mutation within amyloid precursor protein modulates global gene expression towards the pathogenesis of Alzheimer’s disease. BMB Rep 43(10):704–709
Park J, Madan M, Chigurupati S, Baek SH, Cho Y, Mughal MR, Yu A, Chan SL, Pattisapu JV, Mattson MP, Jo DG (2021) Neuronal aquaporin 1 inhibits amyloidogenesis by suppressing the interaction between beta-secretase and amyloid precursor protein. J Gerontol A Biol Sci Med Sci 76(1):23–31
Xu Z, Xiao N, Chen Y, Huang H, Marshall C, Gao J, Cai Z, Wu T, Hu G, Xiao M (2015) Deletion of aquaporin-4 in APP/PS1 mice exacerbates brain Aβ accumulation and memory deficits. Mol Neurodegener 10:58
Yang W, Wu Q, Yuan C, Gao J, Xiao M, Gu M, Ding J, Hu G (2012) Aquaporin-4 mediates astrocyte response to β-amyloid. Mol Cell Neurosci 49(4):406–414
Lan YL, Fang DY, Zhao J, Ma TH, Li S (2016) A research update on the potential roles of aquaporin 4 in neuroinflammation. Acta Neurol Belg 116(2):127–134
Lan YL, Zou S, Chen JJ, Zhao J, Li S (2016) The neuroprotective effect of the association of aquaporin-4/glutamate transporter-1 against Alzheimer’s disease. Neural Plast 2016:4626593
Taoka T, Masutani Y, Kawai H, Nakane T, Matsuoka K, Yasuno F, Kishimoto T, Naganawa S (2017) Evaluation of glymphatic system activity with the diffusion MR technique: diffusion tensor image analysis along the perivascular space (DTI-ALPS) in Alzheimer’s disease cases. Jpn J Radiol 35(4):172–178
Zeppenfeld DM, Simon M, Haswell JD, D'Abreo D, Murchison C, Quinn JF, Grafe MR, Woltjer RL, Kaye J, Iliff JJ (2017) Association of perivascular localization of aquaporin-4 with cognition and Alzheimer disease in aging brains. JAMA Neurol 74(1):91–99
Burfeind KG, Murchison CF, Westaway SK, Simon MJ, Erten-Lyons D, Kaye JA, Quinn JF, Iliff JJ (2017) The effects of noncoding aquaporin-4 single-nucleotide polymorphisms on cognition and functional progression of Alzheimer’s disease. Alzheimers Dement 3(3):348–359
Ulv Larsen SM, Landolt HP, Berger W, Nedergaard M, Knudsen GM, Holst SC (2020) Haplotype of the astrocytic water channel AQP4 is associated with slow wave energy regulation in human NREM sleep. PLoS Biol 18(5):e3000623
Nesic O, Lee J, Unabia G, Johnson K, Ye Z, Vergara L, Hulsebosch C, Perez-Polo J (2008) Aquaporin 1–a novel player in spinal cord injury. J Neurochem 105(3):628–640
Kim JH, Lee YW, Park KA, Lee WT, Lee JE (2010) Agmatine attenuates brain edema through reducing the expression of aquaporin-1 after cerebral ischemia. J Cereb Blood Flow Metab 30(5):943–949
Akdemir G, Kaymaz F, Gursoy-Özdemir Y, Akalan N, Akdemir ES (2016) The time course changes in expression of aquaporin 4 and aquaporin 1 following global cerebral ischemic edema in rat. Surg Neurol Int 7:4
Sánchez Gomar I, Díaz Sánchez M, Uclés Sánchez AJ, Casado Chocán JL, Suárez-Luna N, Ramírez-Lorca R, Villadiego J, Toledo-Aral JJ, Echevarría M (2016) Comparative analysis for the presence of IgG anti-aquaporin-1 in patients with NMO-spectrum disorders. Int J Mol Sci 17(8):1195
Li L, Zhang H, Varrin-Doyer M, Zamvil SS, Verkman A (2011) Proinflammatory role of aquaporin-4 in autoimmune neuroinflammation. FASEB J 25(5):1556–1566
Akdemir G, Ratelade J, Asavapanumas N, Verkman AS (2014) Neuroprotective effect of aquaporin-4 deficiency in a mouse model of severe global cerebral ischemia produced by transient 4-vessel occlusion. Neurosci Lett 574:70–75
Liang F, Luo C, Xu G, Su F, He X, Long S, Ren H, Liu Y, Feng Y, Pei Z (2015) Deletion of aquaporin-4 is neuroprotective during the acute stage of micro traumatic brain injury in mice. Neurosci Lett 598:29–35
Chi Y, Fan Y, He L, Liu W, Wen X, Zhou S, Wang X, Zhang C, Kong H, Sonoda L, Tripathi P, Li CJ, Yu MS, Su C, Hu G (2011) Novel role of aquaporin-4 in CD4+CD25+ T regulatory cell development and severity of parkinson’s disease. Aging Cell 10(3):368–382
Lu DC, Zhang H, Zador Z, Verkman AS (2008) Impaired olfaction in mice lacking aquaporin-4 water channels. FASEB J 22(9):3216–3223
Nicchia GP, Pisani F, Simone L, Cibelli A, Mola MG, Dal Monte M, Frigeri A, Bagnoli P, Svelto M (2016) Glio-vascular modifications caused by Aquaporin-4 deletion in the mouse retina. Exp Eye Res 146:259–268
Zhang Y, Xu K, Liu Y, Erokwu BO, Zhao P, Flask CA, Ramos-Estebanez C, Farr GW, LaManna JC, Boron WF, Yu X (2019) Increased cerebral vascularization and decreased water exchange across the blood-brain barrier in aquaporin-4 knockout mice. PLoS One 14(6):e0218415
Papadopoulos MC, Verkman AS (2008) Potential utility of aquaporin modulators for therapy of brain disorders. Prog Brain Res 170:589–601
Zelenina M (2010) Regulation of brain aquaporins. Neurochem Int 57(4):468–488
Yu LS, Fan YY, Ye G, Li J, Feng XP, Lin K, Dong M, Wang Z (2016) Curcumin alleviates brain edema by lowering AQP4 expression levels in a rat model of hypoxia-hypercapnia-induced brain damage. Exp Ther Med 11(3):709–716
Yukutake Y, Tsuji S, Hirano Y, Adachi T, Takahashi T, Fujihara K, Agre P, Yasui M, Suematsu M (2008) Mercury chloride decreases the water permeability of aquaporin-4-reconstituted proteoliposomes. Biol Cell 100(6):355–363
Migliati E, Meurice N, DuBois P, Fang JS, Somasekharan S, Beckett E, Flynn G, Yool AJ (2009) Inhibition of aquaporin-1 and aquaporin-4 water permeability by a derivative of the loop diuretic bumetanide acting at an internal pore-occluding binding site. Mol Pharmacol 76(1):105–112
Cao S, Zhu P, Yu X, Chen J, Li J, Yan F, Wang L, Yu J, Chen G (2016) Hydrogen sulfide attenuates brain edema in early brain injury after subarachnoid hemorrhage in rats: Possible involvement of MMP-9 induced blood-brain barrier disruption and AQP4 expression. Neurosci Lett 621:88–97
Warth A, Mittelbronn M, Wolburg H (2005) Redistribution of the water channel protein aquaporin-4 and the K+ channel protein Kir4.1 differs in low-and high-grade human brain tumors. Acta Neuropathol 109(4):418–426
Wolburg H, Noell S, Wolburg-Buchholz K, Mack A, Fallier-Becker P (2009) Agrin, aquaporin-4, and astrocyte polarity as an important feature of the blood-brain barrier. Neuroscientist 15(2):180–193
Harrison IF, Ismail O, Machhada A, Colgan N, Ohene Y, Nahavandi P, Ahmed Z, Fisher A, Meftah S, Murray TK, Ottersen OP, Nagelhus EA, O'Neill MJ, Wells JA, Lythgoe MF (2020) Impaired glymphatic function and clearance of tau in an Alzheimer’s disease model. Brain 143(8):2576–2593
Xiao M, Hu G (2014) Involvement of aquaporin 4 in astrocyte function and neuropsychiatric disorders. CNS Neurosci Ther 20(5):385–390
Jakovcevski M, Akbarian S, Di Benedetto B (2016) Pharmacological modulation of astrocytes and the role of cell type-specific histone modifications for the treatment of mood disorders. Curr Opin Pharmacol 26:61–66
Amiry-Moghaddam M, Hoddevik EH, Ottersen OP (2010) Aquaporins: multifarious roles in brain. Neuroscience 168(4):859–861
Azad TD, Pan J, Connolly ID, Remington A, Wilson CM, Grant GA (2015) Therapeutic strategies to improve drug delivery across the blood-brain barrier. Neurosurg Focus 38(3):E9