Advertisement
Research Article| Volume 276, ISSUE 1-2, P103-107, January 15, 2009

Upregulation of water channel aquaporin-4 in experimental autoimmune encephalomyeritis

      Abstract

      Aquaporin-4 (AQP4) is a water channel protein that plays an important role in water movement in the central nervous system (CNS). Recently, presence of anti-AQP4 antibody has been reported in the sera from patients with neuromyelitis optica. AQP4 is therefore a possible target for inflammatory mechanisms in CNS. In the present investigation, we performed semi-quantitative analysis of AQP4-mRNA in brain and spinal cord from mice affected with experimental autoimmune encephalomyelitis (EAE) using real-time PCR. AQP4-mRNA expression was increased in EAE; reaching a peak in the spinal cord at 14 days, and in the brain at 21 days after first inoculation. Immunohistochemical analysis showed that AQP4 is expressed on astrocytes, indicating that the increase in AQP4 expression may correlate with astrocytic activation. This is the first study to demonstrate upregulation of AQP4 in EAE. The upregulation of AQP4 could be involved in the development of inflammation in the acute phase of EAE.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of the Neurological Sciences
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Lehmann G.L.
        • Gradilone S.A.
        • Marinelli R.A.
        Aquaporin water channels in central nervous system.
        Curr Neurovasc Res. 2004; 1: 293-303
        • Nielsen S.
        • Smith B.L.
        • Christensen E.I.
        • Agre P.
        Distribution of the aquaporin CHIP in secretory and resorptive epithelia and capillary endothelia.
        Proc Natl Acad Sci USA. 1993; 90: 7275-7279
        • Venero J.L.
        • Vizuete M.L.
        • Machado A.
        • Cano J.
        Aquaporins in the central nervous system.
        Prog Neurobiol. 2001; 63: 321-336
        • Hasegawa H.
        • Ma T.
        • Skach W.
        • Matthay M.A.
        • Verkman A.S.
        Molecular cloning of a mercurial-insensitive water channel expressed in selected water-transporting tissues.
        J Biol Chem. 1994; 269: 5497-5500
        • Jung J.S.
        • Bhat R.V.
        • Preston G.M.
        • Guggino W.B.
        • Baraban J.M.
        • Agre P.
        Molecular characterization of an aquaporin cDNA from brain: candidate osmoreceptor and regulator of water balance.
        Proc Natl Acad Sci USA. 1994; 91: 13052-13056
        • Frigeri A.
        • Gropper M.A.
        • Turck C.W.
        • Verkman A.S.
        Immunolocalization of the mercurial-insensitive water channel and glycerol intrinsic protein in epithelial cell plasma membranes.
        Proc Natl Acad Sci USA. 1995; 92: 4328-4331
        • Nielsen S.
        • Nagelhus E.A.
        • Amiry-Moghaddam M.
        • Bourque C.
        • Agre P.
        • Ottersen P.
        Specialized membrane domains for water transport in glial cells: high-resolution immunogold cytochemistry of aquaporin-4 in rat brain.
        J Neurosci. 1997; 17: 171-180
        • Venero J.L.
        • Vizuete M.L.
        • Ilundain A.A.
        • Machado A.
        • Echevarria M.
        • Cano J.
        Detailed localization of aquaporin-4 messenger RNA in the CNS: preferential expression in periventricular organs.
        Neuroscience. 1999; 94: 239-250
        • Speake T.
        • Freeman L.J.
        • Brown P.D.
        Expression of aquaporin 1 and aquaporin 4 water channels in rat choroid plexus.
        Biochim Biophys Acta. 2003; 1609: 80-86
        • Aoki K.
        • Uchihara T.
        • Tsuchiya K.
        • Nakamura A.
        • Ikeda K.
        • Wakayama Y.
        Enhanced expression of aquaporin 4 in human brain with infarction.
        Acta Neuropathol. 2003; 106: 121-124
        • Saadoun S.
        • Papadopoulos M.C.
        • Davies D.C.
        • Krishna S.
        • Bell B.A.
        Aquaporin-4 expression is increased in oedematous human brain tumours.
        J Neurol Neurosurg Psychiatry. 2002; 72: 262-265
        • Saadoun S.
        • Papadopoulos M.C.
        • Krishna S.
        Water transport becomes uncoupled from K+ siphoning in brain contusion, bacterial meningitis, and brain tumors: immunohistochemical case review.
        J Clin Pathol. 2003; 12: 972-975
        • Aoki-Yoshino K.
        • Uchihara T.
        • Duyckaerts C.
        • Nakamura A.
        • Hauw J.J.
        • Wakayama Y.
        Enhanced expression of aquaporin 4 in human brain with inflammatory diseases.
        Acta Neuropathol. 2005; 110: 281-288
        • Taniguchi M.
        • Yamashita T.
        • Kumura E.
        • Tamatani M.
        • Kobayashi A.
        • Yokawa T.
        • et al.
        Induction of aquaporin-4 water channel mRNA after focal ischemia in rat.
        Mol Brain Res. 2000; 78: 131-137
        • Vizuete M.L.
        • Venero J.L.
        • Vargas C.
        • Ilundain A.A.
        • Echevarria M.
        • Machado A.
        • et al.
        Differential upregulation of aquaporin-4 mRNA expression in reactive astrocytes after brain injury: potential role in brain edema.
        Neurobiol Dis. 1999; 6: 245-258
        • Vajda Z.
        • Promeneur D.
        • Doczi T.
        • Sulyok E.
        • Fr. kiaer J.
        • Ottersen O.P.
        • et al.
        Increased aquqporin-4 immunoreactivity in rat brain in response to systemic hyponatremia.
        Biochem Biophysics Res Commun. 2000; 270: 495-503
        • Nesic O.
        • Lee J.
        • Ye Z.
        • Unabia G.C.
        • Rafati D.
        • Hulsebosch C.E.
        • et al.
        Acute and chronic changes in aquaporin 4 expression after spinal cord injury.
        Neuroscience. 2006; 143: 779-792
        • Manley G.T.
        • Fujimura M.
        • Ma T.
        • Noshita N.
        • Filiz F.
        • Bollen A.W.
        • et al.
        Aquaporin-4 deletion in mice reduces brain edema after acute water intoxication and ischemic stroke.
        Nat Med. 2000; 6: 159-163
        • Marmarou A.
        • Hochwald G.
        • Nakamura T.
        • Tanaka K.
        • Weaver J.
        • Dunbar J.
        Brain edema resolution by CSF pathways and brain vasculature in cats.
        Am J Physiol. 1994; 267: H514-520
        • Chan P.H.
        • Yang G.Y.
        • Chen S.F.
        • Carlson E.
        • Epstein C.J.
        Cold-induced brain edema and infarction are reduced in transgenic mice overexpressing CuZn-superoxide dismutase.
        Ann Neurol. 1991; 29: 482-486
        • Oury T.D.
        • Piantadosi C.A.
        • Crapo J.D.
        Cold-induced brain edema in mice. Involvement of extracellular superoxide dismutase and nitric oxide.
        J Biol Chem. 1993; 268: 394-398
        • Kaye A.H.
        • Morstyn G.
        • Gardner I.
        • Pyke K.
        Development of a xenograft glioma model in mouse brain.
        Cancer Res. 1986; 46: 1367-1373
        • Sampson J.H.
        • Crotty L.E.
        • Lee S.
        • Archer G.E.
        • Ashley D.M.
        • Wikstrand C.J.
        • et al.
        Unarmed, tumor-specific monoclonal antibody effectively treats brain tumors.
        Proc Natl Acad Sci USA. 2000; 97: 7503-7508
        • Papadopoulos M.C.
        • Manley G.T.
        • Krishna S.
        • Verkman A.S.
        Aquaporin-4 facilitates reabsorption of excess fluid in vasogenic brain edema.
        FASEB J. 2004; 18: 1291-1293
        • Misu T.
        • Fujihara K.
        • Nakashima I.
        • Miyazawa I.
        • Okita N.
        • Takase S.
        • et al.
        Pure optic-spinal form of multiple sclerosis in Japan.
        Brain. 2002; 125: 2460-2468
        • Lennon V.A.
        • Wingerchuk D.M.
        • Kryzer T.J.
        • Pittock S.J.
        • Lucchinetti C.F.
        • Fujihara K.
        • et al.
        A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis.
        Lancet. 2004; 364: 2106-2112
        • Lennon V.A.
        • Kryzer T.J.
        • Pittock S.J.
        • Verkman A.S.
        • Hinson S.R.
        IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel.
        J Exp Med. 2005; 202: 473-477
        • Matsuoka T.
        • Matsushita T.
        • Kawano Y.
        • Osoegawa M.
        • Ochi H.
        • Ishizu T.
        • et al.
        Heterogeneity of aquaporin-4 autoimmunity and spinal cord lesions in multiple sclerosis in Japanese.
        Brain. 2007; 130: 1206-1223
        • Kuroiwa Y.
        Neuromyelitis optica (Devic's disease, Devic's syndrome).
        in: Handbook of clinical neurology. Demyelinating disease. Elsevier Science Publishers, 1985: 397-408
        • Misu T.
        • Fujihara K.
        • Kakita A.
        • Konno H.
        • Nakamura M.
        • Watanabe S.
        • et al.
        Loss of aquaporin 4 in lesions of neuromyelitis optica: distinction from multiple sclerosis.
        Brain. 2007; 130: 1224-1234
        • Miyamoto K.
        • Miyake S.
        • Yamamura T.
        A synthetic glycolipid prevents autoimmune encephalomyelitis by inducing TH2 bias of natural killer T cells.
        Nature. 2001; 413: 531-534
        • Miyamoto K.
        • Miyake S.
        • Schachner M.
        • Yamamura T.
        Heterozygous null mutation of myelin P0 protein enhances susceptibility to autoimmune neuritis targeting P0 peptide.
        Eur J Immunol. 2003; 33: 656-665
        • Sinclair C.
        • Kirk J.
        • Herron B.
        • Fitzgerald U.
        • McQuaid S.
        Absence of aquaporin-4 expression in lesions of neuromyelitis optica but increased expression in multiple sclerosis lesions and normal-appearing white matter.
        Acta Neuropathol. 2007; 113: 187-194