Skip to main content

Advertisement

SpringerLink
Log in

The potential roles of aquaporin 4 in amyotrophic lateral sclerosis

  • Review Article
  • Published:
Neurological Sciences Aims and scope Submit manuscript

Abstract

Aquaporin 4 (AQP4) is a primary water channel found on astrocytes in the central nervous system (CNS). Besides its function in water and ion homeostasis, AQP4 has also been documented to be involved in a myriad of acute and chronic cerebral pathologies, including autoimmune neurodegenerative diseases. AQP4 has been postulated to be associated with the incidence of a progressive neurodegenerative disorder known as amyotrophic lateral sclerosis (ALS), a disease that targets the motor neurons, causing muscle weakness and eventually paralysis. Raised AQP4 levels were noted in association with vessels surrounded with swollen astrocytic processes as well as in the brainstem, cortex, and gray matter in patients with terminal ALS. AQP4 depolarization may lead to motor neuron degeneration in ALS via GLT-1. Besides, alterations in AQP4 expression in ALS may result in the loss of blood–brain barrier (BBB) integrity. Changes in AQP4 function may also disrupt K+ homeostasis and cause connexin dysregulation, the latter of which is associated to ALS disease progression. Furthermore, AQP4 suppression augments recovery in motor function in ALS, a phenomenon thought to be associated to NGF. No therapeutic drug targeting AQP4 has been developed to date. Nevertheless, the plethora of suggestive experimental results underscores the significance of further exploration into this area.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Papadopoulos MC, Verkman AS (2007) Aquaporin-4 and brain edema. Pediatr Nephrol 22:778–784

    Article  PubMed  PubMed Central  Google Scholar 

  2. Manley GT, Fujimura M, Ma T, Noshita N, Filiz F, Bollen AW, Chan P, Verkman AS (2000) Aquaporin-4 deletion in mice reduces brain edema after acute water intoxication and ischemic stroke. Nat Med 6:159–163

    Article  CAS  PubMed  Google Scholar 

  3. Xu M, Xiao M, Li S, Yang B (2017) Aquaporins in nervous system. Adv Exp Med Biol 969:81–103

    Article  CAS  PubMed  Google Scholar 

  4. 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 53:631–636

    Article  PubMed  Google Scholar 

  5. Binder DK, Oshio K, Ma T, Verkman AS, Manley GT (2004) Increased seizure threshold in mice lacking aquaporin-4 water channels. Neuroreport 15:259–262

    Article  CAS  PubMed  Google Scholar 

  6. Rama Rao KV, Chen M, Simard JM, Norenberg MD (2003) Increased aquaporin-4 expression in ammonia-treated cultured astrocytes. Neuroreport 14:2379–2382

    Article  CAS  PubMed  Google Scholar 

  7. Papadopoulos MC, Saadoun S, Binder DK, Manley GT, Krishna S, Verkman AS (2004) Molecular mechanisms of brain tumor edema. Neuroscience 129:1011–1020

    Article  CAS  PubMed  Google Scholar 

  8. Hamby ME, Sofroniew MV (2010) Reactive astrocytes as therapeutic targets for CNS disorders. Neurotherapeutics 7:494–506

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Thrane AS, Rappold PM, Fujita T, Torres A, Bekar LK, Takano T, Peng W, Wang F, Rangroo Thrane V, Enger R, Haj-Yasein NN, Skare O, Holen T, Klungland A, Ottersen OP, Nedergaard M, Nagelhus EA (2011) Critical role of aquaporin-4 (AQP4) in astrocytic Ca2+ signaling events elicited by cerebral edema. Proc Natl Acad Sci U S A 108:846–851

    Article  PubMed  Google Scholar 

  10. 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 121:4029–4036

    Article  CAS  PubMed  Google Scholar 

  11. 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

    Article  CAS  PubMed  Google Scholar 

  12. MacAulay N, Zeuthen T (2010) Water transport between CNS compartments: contributions of aquaporins and cotransporters. Neuroscience 168:941–956

    Article  CAS  PubMed  Google Scholar 

  13. Auguste KI, Jin S, Uchida K, Yan D, Manley GT, Papadopoulos MC, Verkman AS (2007) Greatly impaired migration of implanted aquaporin-4-deficient astroglial cells in mouse brain toward a site of injury. FASEB J 21:108–116

    Article  CAS  PubMed  Google Scholar 

  14. Papadopoulos MC, Saadoun S, Verkman AS (2008) Aquaporins and cell migration. Pflugers Arch 456:693–700

    Article  CAS  PubMed  Google Scholar 

  15. 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 82:458–464

    Article  CAS  PubMed  Google Scholar 

  16. Li L, Zhang H, Varrin-Doyer M, Zamvil SS, Verkman AS (2011) Proinflammatory role of aquaporin-4 in autoimmune neuroinflammation. FASEB J 25:1556–1566

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Benfenati V, Ferroni S (2010) Water transport between CNS compartments: functional and molecular interactions between aquaporins and ion channels. Neuroscience 168:926–940

    Article  CAS  PubMed  Google Scholar 

  18. Hubbard JA, Szu JI, Binder DK (2017) The role of aquaporin-4 in synaptic plasticity, memory and disease. Brain Res Bull 136:118–129

    Article  CAS  PubMed  Google Scholar 

  19. Di Giorgio FP, Carrasco MA, Siao MC, Maniatis T, Eggan K (2007) Non-cell autonomous effect of glia on motor neurons in an embryonic stem cell-based ALS model. Nat Neurosci 10:608–614

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Amin Lari A, Ghavanini AA, Bokaee HR (2019) A review of electrophysiological studies of lower motor neuron involvement in amyotrophic lateral sclerosis. Neurol Sci. https://doi.org/10.1007/s10072-019-03832-4

  21. Benfenati V, Nicchia GP, Svelto M, Rapisarda C, Frigeri A, Ferroni S (2007) Functional down-regulation of volume-regulated anion channels in AQP4 knockdown cultured rat cortical astrocytes. J Neurochem 100:87–104

    Article  CAS  PubMed  Google Scholar 

  22. Kaiser M, Maletzki I, Hulsmann S, Holtmann B, Schulz-Schaeffer W, Kirchhoff F, Bahr M, Neusch C (2006) Progressive loss of a glial potassium channel (KCNJ10) in the spinal cord of the SOD1 (G93A) transgenic mouse model of amyotrophic lateral sclerosis. J Neurochem 99:900–912

    Article  CAS  PubMed  Google Scholar 

  23. Nicaise C, Soyfoo MS, Authelet M, De Decker R, Bataveljic D, Delporte C, Pochet R (2009) Aquaporin-4 overexpression in rat ALS model. Anat Rec (Hoboken) 292:207–213

    Article  CAS  Google Scholar 

  24. Hoshi A, Tsunoda A, Yamamoto T, Tada M, Kakita A, Ugawa Y (2018) Altered expression of glutamate transporter-1 and water channel protein aquaporin-4 in human temporal cortex with Alzheimer's disease. Neuropathol Appl Neurobiol 44:628–638

    Article  CAS  PubMed  Google Scholar 

  25. Jimi T, Wakayama Y, Matsuzaki Y, Hara H, Inoue M, Shibuya S (2004) Reduced expression of aquaporin 4 in human muscles with amyotrophic lateral sclerosis and other neurogenic atrophies. Pathol Res Pract 200:203–209

    Article  CAS  PubMed  Google Scholar 

  26. Dai J, Lin W, Zheng M, Liu Q, He B, Luo C, Lu X, Pei Z, Su H, Yao X (2017) Alterations in AQP4 expression and polarization in the course of motor neuron degeneration in SOD1G93A mice. Mol Med Rep 16:1739–1746

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. 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 alpha-syntrophiN-null mice. Proc Natl Acad Sci U S A 100:13615–13620

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Haj-Yasein NN, Jensen V, Østby I, Omholt SW, Voipio J, Kaila K, Ottersen OP, Hvalby Ø, Nagelhus EA (2012) Aquaporin-4 regulates extracellular space volume dynamics during high-frequency synaptic stimulation: a gene deletion study in mouse hippocampus. Glia 60:867–874

    Article  PubMed  Google Scholar 

  29. Wei F, Zhang C, Xue R, Shan L, Gong S, Wang G, Tao J, Xu G, Zhang G, Wang L (2017) The pathway of subarachnoid CSF moving into the spinal parenchyma and the role of astrocytic aquaporin-4 in this process. Life Sci 182:29–40

    Article  CAS  PubMed  Google Scholar 

  30. Li Y, Gu R, Zhu Q, Liu J (2018) Changes of spinal edema and expression of aquaporin 4 in methylprednisolone-treated rats with spinal cord injury. Ann Clin Lab Sci 48:453–459

    CAS  PubMed  Google Scholar 

  31. Oklinski MK, Lim JS, Choi HJ, Oklinska P, Skowronski MT, Kwon TH (2014) Immunolocalization of water channel proteins AQP1 and AQP4 in rat spinal cord. J Histochem Cytochem 62:598–611

    Article  CAS  PubMed  Google Scholar 

  32. Maragakis NJ, Rothstein JD (2006) Mechanisms of disease: astrocytes in neurodegenerative disease. Nat Clin Pract Neurol 2:679–689

    Article  CAS  PubMed  Google Scholar 

  33. Maragakis NJ, Rothstein JD (2004) Glutamate transporters: animal models to neurologic disease. Neurobiol Dis 15:461–473

    Article  CAS  PubMed  Google Scholar 

  34. Rothstein JD, Martin LJ, Kuncl RW (1992) Decreased glutamate transport by the brain and spinal cord in amyotrophic lateral sclerosis. N Engl J Med 326:1464–1468

    Article  CAS  PubMed  Google Scholar 

  35. Rothstein JD, Van Kammen M, Levey AI, Martin LJ, Kuncl RW (1995) Selective loss of glial glutamate transporter GLT-1 in amyotrophic lateral sclerosis. Ann Neurol 38:73–84

    Article  CAS  PubMed  Google Scholar 

  36. Howland DS, Liu J, She Y, Goad B, Maragakis NJ, Kim B, Erickson J, Kulik J, DeVito L, Psaltis G, DeGennaro LJ, Cleveland DW, Rothstein JD (2002) Focal loss of the glutamate transporter EAAT2 in a transgenic rat model of SOD1 mutant-mediated amyotrophic lateral sclerosis (ALS). Proc Natl Acad Sci U S A 99:1604–1609

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Lan YL, Zhao J, Ma T, Li S (2016) The potential roles of aquaporin 4 in Alzheimer’s disease. Mol Neurobiol 53:5300–5309

    Article  CAS  PubMed  Google Scholar 

  38. 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Lan YL, Chen JJ, Hu G, Xu J, Xiao M, Li S (2017) Aquaporin 4 in astrocytes is a target for therapy in Alzheimer’s disease. Curr Pharm Des 23:4948–4957

    CAS  PubMed  Google Scholar 

  40. Yang J, Li MX, Luo Y, Chen T, Liu J, Fang P, Jiang B, Hu ZL, Jin Y, Chen JG, Wang F (2013) Chronic ceftriaxone treatment rescues hippocampal memory deficit in AQP4 knockout mice via activation of GLT-1. Neuropharmacology 75:213–222

    Article  CAS  PubMed  Google Scholar 

  41. Hinson SR, Roemer SF, Lucchinetti CF, Fryer JP, Kryzer TJ, Chamberlain JL, Howe CL, Pittock SJ, Lennon VA (2008) Aquaporin-4-binding autoantibodies in patients with neuromyelitis optica impair glutamate transport by down-regulating EAAT2. J Exp Med 205:2473–2481

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Mandrioli J, Rosi E, Fini N, Fasano A, Raggi S, Fantuzzi AL, Bedogni G (2017) Changes in routine laboratory tests and survival in amyotrophic lateral sclerosis. Neurol Sci 38:2177–2182

    Article  PubMed  Google Scholar 

  43. Forte G, Bocca B, Oggiano R, Clemente S, Asara Y, Sotgiu MA, Farace C, Montella A, Fois AG, Malaguarnera M, Pirina P, Madeddu R (2017) Essential trace elements in amyotrophic lateral sclerosis (ALS): results in a population of a risk area of Italy. Neurol Sci 38:1609–1615

    Article  PubMed  Google Scholar 

  44. Nakata M, Kuwabara S, Kanai K, Misawa S, Tamura N, Sawai S, Hattori T, Bostock H (2006) Distal excitability changes in motor axons in amyotrophic lateral sclerosis. Clin Neurophysiol 117:1444–1448

    Article  CAS  PubMed  Google Scholar 

  45. Kanai K, Kuwabara S, Arai K, Sung JY, Ogawara K, Hattori T (2003) Muscle cramp in Machado-Joseph disease: altered motor axonal excitability properties and mexiletine treatment. Brain 126:965–973

    Article  PubMed  Google Scholar 

  46. Newman EA, Frambach DA, Odette LL (1984) Control of extracellular potassium levels by retinal glial cell K+ siphoning. Science 225:1174–1175

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Bataveljić D, Nikolić L, Milosević M, Todorović N, Andjus PR (2012) Changes in the astrocytic aquaporin-4 and inwardly rectifying potassium channel expression in the brain of the amyotrophic lateral sclerosis SOD1(G93A) rat model. Glia 60:1991–2003

    Article  PubMed  Google Scholar 

  48. Nagelhus EA, Mathiisen TM, Ottersen OP (2004) Aquaporin-4 in the central nervous system: cellular and subcellular distribution and coexpression with Kir4.1. Neuroscience 129:905–913

    Article  CAS  PubMed  Google Scholar 

  49. Jo AO, Ryskamp DA, Phuong TT, 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 35:13525–13537

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Zlokovic BV (2008) The blood-brain barrier in health and chronic neurodegenerative disorders. Neuron 57:178–201

    Article  CAS  PubMed  Google Scholar 

  51. Garbuzova-Davis S, Saporta S, Haller E, Kolomey I, Bennett SP, Potter H, Sanberg PR (2007) Evidence of compromised blood-spinal cord barrier in early and late symptomatic SOD1 mice modeling ALS. PLoS One 2:e1205

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Zhong Z, Deane R, Ali Z, Parisi M, Shapovalov Y, O’Banion MK, Stojanovic K, Sagare A, Boillee S, Cleveland DW, Zlokovic BV (2008) ALS-causing SOD1 mutants generate vascular changes prior to motor neuron degeneration. Nat Neurosci 11:420–422

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Garbuzova-Davis S, Haller E, Saporta S, Kolomey I, Nicosia SV, Sanberg PR (2007) Ultrastructure of blood-brain barrier and blood-spinal cord barrier in SOD1 mice modeling ALS. Brain Res 1157:126–137

    Article  CAS  PubMed  Google Scholar 

  54. Steiner J, Bogerts B, Schroeter ML, Bernstein HG (2011) S100B protein in neurodegenerative disorders. Clin Chem Lab Med 49:409–424

    Article  CAS  PubMed  Google Scholar 

  55. Wu YF, Sytwu HK, Lung FW (2018) Human aquaporin 4 gene polymorphisms and haplotypes are associated with serum S100B level and negative symptoms of schizophrenia in a southern Chinese Han population. Front Psychiatry 9:657

    Article  PubMed  PubMed Central  Google Scholar 

  56. Yu YJ, Watts RJ (2013) Developing therapeutic antibodies for neurodegenerative disease. Neurotherapeutics 10:459–472

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Hillebrand S, Schanda K, Nigritinou M, Tsymala I, Böhm D, Peschl P, Takai Y, Fujihara K, Nakashima I, Misu T, Reindl M, Lassmann H, Bradl M (2019) Circulating AQP4-specific auto-antibodies alone can induce neuromyelitis optica spectrum disorder in the rat. Acta Neuropathol 137:467–485

    Article  CAS  PubMed  Google Scholar 

  58. Howe CL, Kaptzan T, Magana SM, Ayers-Ringler JR, LaFrance-Corey RG, Lucchinetti CF (2014) Neuromyelitis optica IgG stimulates an immunological response in rat astrocyte cultures. Glia 62:692–708

    Article  PubMed  PubMed Central  Google Scholar 

  59. Takeshita Y, Obermeier B, Cotleur AC, Spampinato SF, Shimizu F, Yamamoto E, Sano Y, Kryzer TJ, Lennon VA, Kanda T, Ransohoff RM (2017) Effects of neuromyelitis optica-IgG at the blood–brain barrier in vitro. Neurol Neuroimmunol Neuroinflammation 4:e311

    Article  Google Scholar 

  60. 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 19:1–5

    Article  PubMed  Google Scholar 

  61. Saadoun S, Tait MJ, Reza A, Davies DC, Bell BA, Verkman AS, Papadopoulos MC (2009) AQP4 gene deletion in mice does not alter blood-brain barrier integrity or brain morphology. Neuroscience 161:764–772

    Article  CAS  PubMed  Google Scholar 

  62. Eilert-Olsen M, Haj-Yasein NN, Vindedal GF, Enger R, Gundersen GA, Hoddevik EH, Petersen PH, Haug FMS, Skare Ø, Adams ME, Froehner SC, Burkhardt JM, Thoren AE, Nagelhus EA (2012) Deletion of aquaporin-4 changes the perivascular glial protein scaffold without disrupting the brain endothelial barrier. Glia 60:432–440

    Article  PubMed  Google Scholar 

  63. Feng X, Papadopoulos MC, Liu J, Li L, Zhang D, Zhang H, Verkman AS, Ma T (2009) Sporadic obstructive hydrocephalus in Aqp4 null mice. J Neurosci Res 87:1150–1155

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Lin X, Xu Q, Veenstra RD (2014) Functional formation of heterotypic gap junction channels by connexins-40 and -43. Channels (Austin) 8:433–443

    Article  Google Scholar 

  65. Orthmann-Murphy JL, Abrams CK, Scherer SS (2008) Gap junctions couple astrocytes and oligodendrocytes. J Mol Neurosci 35:101–116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Díaz-Amarilla P, Olivera-Bravo S, Trias E, Cragnolini A, Martínez-Palma L, Cassina P, Beckman J, Barbeito L (2011) Phenotypically aberrant astrocytes that promote motoneuron damage in a model of inherited amyotrophic lateral sclerosis. Proc Natl Acad Sci U S A 108:18126–18131

    Article  PubMed  PubMed Central  Google Scholar 

  67. Cui Y, Masaki K, Yamasaki R, Imamura S, Suzuki SO, Hayashi S, Sato S, Nagara Y, Kawamura MF, Kira J (2014) Extensive dysregulations of oligodendrocytic and astrocytic connexins are associated with disease progression in an amyotrophic lateral sclerosis mouse model. J Neuroinflammation 11:42

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Rash JE, Yasumura T, Dudek FE, Nagy JI (2001) Cell-specific expression of connexins and evidence of restricted gap junctional coupling between glial cells and between neurons. J Neurosci 21:1983–2000

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Griemsmann S, Höft SP, Bedner P et al (2015) Characterization of panglial gap junction networks in the thalamus, neocortex, and hippocampus reveals a unique population of glial cells. Cereb Cortex 25:3420–3433

    Article  PubMed  Google Scholar 

  70. Katoozi S, Skauli N, Rahmani S, Camassa LMA, Boldt HB, Ottersen OP, Amiry-Moghaddam M (2017) Targeted deletion of Aqp4 promotes the formation of astrocytic gap junctions. Brain Struct Funct 222:3959–3972

    Article  CAS  PubMed  Google Scholar 

  71. Strohschein S, Huttmann K, Gabriel S, Binder DK, Heinemann U, Steinhauser C (2011) Impact of aquaporin-4 channels on K+ buffering and gap junction coupling in the hippocampus. Glia 59:973–980

    Article  PubMed  Google Scholar 

  72. Li G, Liu X, Liu Z, Su Z (2015) Interactions of connexin 43 and aquaporin-4 in the formation of glioma-induced brain edema. Mol Med Rep 11:1188–1194

    Article  CAS  PubMed  Google Scholar 

  73. Hu AM, Li JJ, Sun W et al (2015) Myelotomy reduces spinal cord edema and inhibits aquaporin-4 and aquaporin-9 expression in rats with spinal cord injury. Spinal Cord 53:98–102

    Article  PubMed  Google Scholar 

  74. Nesic O, Lee J, Ye Z, Unabia GC, Rafati D, Hulsebosch CE, Perez-Polo JR (2006) Acute and chronic changes in aquaporin 4 expression after spinal cord injury. Neuroscience 143:779–792

    Article  CAS  PubMed  Google Scholar 

  75. 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 49:1327–1337

    Article  CAS  PubMed  Google Scholar 

  76. Mao L, Wang HD, Pan H, Qiao L (2011) Sulphoraphane enhances aquaporin-4 expression and decreases spinal cord oedema following spinal cord injury. Brain Inj 25:300–306

    Article  PubMed  Google Scholar 

  77. Saadoun S, Bell BA, Verkman AS, Papadopoulos MC (2008) Greatly improved neurological outcome after spinal cord compression injury in AQP4-deficient mice. Brain 131:1087–1098

    Article  PubMed  Google Scholar 

  78. 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 67:794–801

    PubMed  Google Scholar 

  79. Nesic O, Guest JD, Zivadinovic D, Narayana PA, Herrera JJ, Grill RJ, Mokkapati VU, Gelman BB, Lee J (2010) Aquaporins in spinal cord injury: the janus face of aquaporin 4. Neuroscience 168:1019–1035

    Article  CAS  PubMed  Google Scholar 

  80. Ferreira D, Westman E, Eyjolfsdottir H et al (2015) Brain changes in Alzheimer’s disease patients with implanted encapsulated cells releasing nerve growth factor. J Alzheimers Dis 43:1059–1072

    Article  CAS  PubMed  Google Scholar 

  81. Appel SH (1981) A unifying hypothesis for the cause of amyotrophic lateral sclerosis, parkinsonism, and Alzheimer disease. Ann Neurol 10:499–505

    Article  CAS  PubMed  Google Scholar 

  82. Anand P, Parrett A, Martin J, Zeman S, Foley P, Swash M, Leigh PN, Cedarbaum JM, Lindsay RM, Williams-Chestnut RE, Sinicropi DV (1995) Regional changes of ciliary neurotrophic factor and nerve growth factor levels in post mortem spinal cord and cerebral cortex from patients with motor disease. Nat Med 1:168–172

    Article  CAS  PubMed  Google Scholar 

  83. Chen J, Zeng X, Li S, Zhong Z, Hu X, Xiang H, Rao Y, Zhang L, Zhou X, Xia Q, Wang T, Zhang X (2017) Lentivirus-mediated inhibition of AQP4 accelerates motor function recovery associated with NGF in spinal cord contusion rats. Brain Res 1669:106–113

    Article  CAS  PubMed  Google Scholar 

  84. Verkman AS, Smith AJ, Phuan PW, Tradtrantip L, Anderson MO (2017) The aquaporin-4 water channel as a potential drug target in neurological disorders. Expert Opin Ther Targets 21:1161–1170

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Author notes

  1. Shuang Zou, Yu-Long Lan and Hongjin Wang contributed equally to this work.

Authors and Affiliations

  1. Computer Center, The Second Affiliated Hospital of Dalian Medical University, 467 Zhong Shan Road, Dalian, 116023, China

    Shuang Zou & Yan-Guo Sun

  2. Department of Neurosurgery, The Second Affiliated Hospital of Dalian Medical University, 467 Zhong Shan Road, Dalian, 116023, China

    Shuang Zou, Yu-Long Lan & Bo Zhang

  3. Department of Neurology, The Second Affiliated Hospital of Dalian Medical University, Dalian, 116011, China

    Shuang Zou & Hongjin Wang

  4. Department of Physiology, Dalian Medical University, Dalian, 116044, China

    Shuang Zou & Yu-Long Lan

  5. Department of Neurosurgery, Shenzhen People’s Hospital, Shenzhen, 518020, China

    Bo Zhang

Authors
  1. Shuang Zou
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yu-Long Lan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hongjin Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bo Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yan-Guo Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Bo Zhang or Yan-Guo Sun.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical standards

This article does not contain any study with human subjects performed by any of the authors.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zou, S., Lan, YL., Wang, H. et al. The potential roles of aquaporin 4 in amyotrophic lateral sclerosis. Neurol Sci 40, 1541–1549 (2019). https://doi.org/10.1007/s10072-019-03877-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10072-019-03877-5

Keywords

Search

Navigation