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Molecular Neurobiology

, Volume 56, Issue 12, pp 8237–8254 | Cite as

Megalencephalic Leukoencephalopathy with Subcortical Cysts Protein-1 (MLC1) Counteracts Astrocyte Activation in Response to Inflammatory Signals

  • Maria Stefania Brignone
  • Angela Lanciotti
  • Barbara Serafini
  • Cinzia Mallozzi
  • Marco Sbriccoli
  • Caterina Veroni
  • Paola Molinari
  • Xabier Elorza-Vidal
  • Tamara Corinna Petrucci
  • Raul Estévez
  • Elena AmbrosiniEmail author
Article
  • 239 Downloads

Abstract

Megalencephalic leukoencephalopathy with subcortical cysts protein-1 (MLC1) is a membrane protein expressed by perivascular astrocytes. MLC1 mutations cause MLC, an incurable leukodystrophy characterized by macrocephaly, brain edema, cysts, myelin vacuolation, and astrocytosis, leading to cognitive/motor impairment and epilepsy. Although its function is unknown, MLC1 favors regulatory volume decrease after astrocyte osmotic swelling and down-regulates intracellular signaling pathways controlling astrocyte activation and proliferation. By combining analysis of human brain tissues with in vitro experiments, here we investigated MLC1 role in astrocyte activation during neuroinflammation, a pathological condition exacerbating patient symptoms. MLC1 upregulation was observed in brain tissues from multiple sclerosis, Alzheimer’s, and Creutzfeld-Jacob disease, all pathologies characterized by strong astrocytosis and release of inflammatory cytokines, particularly IL-1β. Using astrocytoma lines overexpressing wild-type (WT) or mutated MLC1 and astrocytes from control and Mlc1 knock-out (KO) mice, we found that IL-1β stimulated WT-MLC1 plasma membrane expression in astrocytoma cells and control primary astrocytes. In astrocytoma, WT-MLC1 inhibited the activation of IL-1β–induced inflammatory signals (pERK, pNF-kB) that, conversely, were constitutively activated in mutant expressing cells or abnormally upregulated in KO astrocytes. WT-MLC1+ cells also expressed reduced levels of the astrogliosis marker pSTAT3. We then monitored MLC1 expression timing in a demyelinating/remyelinating murine cerebellar organotypic culture model where, after the demyelination and release of inflammatory cytokines, recovery processes occur, revealing MLC1 upregulation in these latter phases. Altogether, these findings suggest that by modulating specific pathways, MLC1 contributes to restore astrocyte homeostasis after inflammation, providing the opportunity to identify drug target molecules to slow down disease progression.

Keywords

Leukodystrophy Neuroinflammation Neurodegeneration IL-1β pERK Astrocytosis 

Notes

Acknowledgments

We thank Dr. Antonella Bernardo for providing rat astrocyte cultures, Dr. Barbara Rosicarelli for technical assistance in the immunohistochemical work, and the UK Multiple Sclerosis Tissue Bank (http://www.imperial.ac.uk/medicine/multiple-sclerosis-and-parkinsons-tissue-bank) for providing brain tissue samples.

Fundings

This work was supported by Italian Ministry of Health, Ricerca Finalizzata, (Grant N. GR-2013-02355882 to A.L.); European Leukodystrophies Association (ELA) (Grant N. ELA 2016-002F3 to M.S.B and ELA2012-014C2B to R.E.); TELETHON (Grant N. GEP14134 to E.A.); Spanish Ministerio de Ciencia e Innovación (MICINN) (SAF2015–70377 to R.E.); and the Generalitat de Catalunya (SGR2014–1178 to R.E.), (ERARE to R.E.). R.E. is a recipient of an ICREA Academia prize.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

12035_2019_1657_MOESM1_ESM.pdf (282 kb)
ESM 1 (PDF 281 kb)
12035_2019_1657_MOESM2_ESM.pdf (547 kb)
ESM 2 (PDF 547 kb)

References

  1. 1.
    Sofroniew MV, Vinters HV (2010) Astrocytes: biology and pathology. Acta Neuropathol 119:7–35CrossRefPubMedGoogle Scholar
  2. 2.
    Pekny M, Pekna M (2014) Astrocyte reactivity and reactive astrogliosis: costs and benefits. Physiol Rev 94:1077–1098CrossRefPubMedGoogle Scholar
  3. 3.
    Pekny M, Wilhelmsson U, Pekna M (2014) The dual role of astrocyte activation and reactive gliosis. Neurosci Lett 565:30–38CrossRefPubMedGoogle Scholar
  4. 4.
    Liddelow SA, Barres BA (2017) Reactive astrocytes: production, function, and therapeutic potential. Immunity. 46:957–967CrossRefPubMedGoogle Scholar
  5. 5.
    Pekny M, Pekna M (2016) Reactive gliosis in the pathogenesis of CNS diseases. Biochim Biophys Acta 1862:483–491CrossRefPubMedGoogle Scholar
  6. 6.
    Pekny M, Pekna M, Messing A, Steinhauser C, Lee JM, Parpura V, Hol EM, Sofroniew MV et al (2016) Astrocytes: a central element in neurological diseases. Acta Neuropathol 131:323–345CrossRefPubMedGoogle Scholar
  7. 7.
    Ben Haim L, Carrillo-de Sauvage MA, Ceyzeriat K, Escartin C (2015) Elusive roles for reactive astrocytes in neurodegenerative diseases. Front Cell Neurosci 9:278CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Ferrer I (2017) Diversity of astroglial responses across human neurodegenerative disorders and brain aging. Brain Pathol 27:645–674CrossRefPubMedGoogle Scholar
  9. 9.
    Lanciotti A, Brignone MS, Bertini E, Petrucci TC, Aloisi F, Ambrosini E (2013) Astrocytes: emerging stars in leukodystrophy pathogenesis. Transl Neurosci 4.  https://doi.org/10.2478/s13380-013-0118-1
  10. 10.
    Leegwater PA, Boor PK, Yuan BQ, van der Steen J, Visser A, Konst AA, Oudejans CB, Schutgens RB et al (2002) Identification of novel mutations in MLC1 responsible for megalencephalic leukoencephalopathy with subcortical cysts. Hum Genet 110:279–283CrossRefPubMedGoogle Scholar
  11. 11.
    Leegwater PA, Yuan BQ, van der Steen J, Mulders J, Konst AA, Boor PK, Mejaski-Bosnjak V, van der Maarel SM et al (2001) Mutations of MLC1 (KIAA0027), encoding a putative membrane protein, cause megalencephalic leukoencephalopathy with subcortical cysts. Am J Hum Genet 68:831–838CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Yalcinkaya C, Yuksel A, Comu S, Kilic G, Cokar O, Dervent A (2003) Epilepsy in vacuolating megalencephalic leukoencephalopathy with subcortical cysts. Seizure. 12:388–396CrossRefPubMedGoogle Scholar
  13. 13.
    van der Knaap MS, Barth PG, Vrensen GF, Valk J (1996) Histopathology of an infantile-onset spongiform leukoencephalopathy with a discrepantly mild clinical course. Acta Neuropathol 92:206–212CrossRefPubMedGoogle Scholar
  14. 14.
    Pascual-Castroviejo I, van der Knaap MS, Pronk JC, Garcia-Segura JM, Gutierrez-Molina M, Pascual-Pascual SI (2005) Vacuolating megalencephalic leukoencephalopathy: 24 year follow-up of two siblings. Neurologia. 20:33–40PubMedGoogle Scholar
  15. 15.
    Duarri A, Lopez de Heredia M, Capdevila-Nortes X, Ridder MC, Montolio M, Lopez-Hernandez T, Boor I, Lien CF et al (2011) Knockdown of MLC1 in primary astrocytes causes cell vacuolation: a MLC disease cell model. Neurobiol Dis 43:228–238CrossRefPubMedGoogle Scholar
  16. 16.
    Ridder MC, Boor I, Lodder JC, Postma NL, Capdevila-Nortes X, Duarri A, Brussaard AB, Estevez R et al (2011) Megalencephalic leucoencephalopathy with cysts: defect in chloride currents and cell volume regulation. Brain. 134:3342–3354CrossRefPubMedGoogle Scholar
  17. 17.
    Dubey M, Bugiani M, Ridder MC, Postma NL, Brouwers E, Polder E, Jacobs JG, Baayen JC et al (2015) Mice with megalencephalic leukoencephalopathy with cysts: a developmental angle. Ann Neurol 77:114–131CrossRefPubMedGoogle Scholar
  18. 18.
    Jayakumar AR, Rao KV, Panickar KS, Moriyama M, Reddy PV, Norenberg MD (2008) Trauma-induced cell swelling in cultured astrocytes. J Neuropathol Exp Neurol 67:417–427CrossRefPubMedGoogle Scholar
  19. 19.
    Pasantes-Morales H, Vazquez-Juarez E (2012) Transporters and channels in cytotoxic astrocyte swelling. Neurochem Res 37:2379–2387CrossRefPubMedGoogle Scholar
  20. 20.
    Brosnan CF, Raine CS (2013) The astrocyte in multiple sclerosis revisited. Glia. 61:453–465CrossRefPubMedGoogle Scholar
  21. 21.
    Bugiani M, Moroni I, Bizzi A, Nardocci N, Bettecken T, Gartner J, Uziel G (2003) Consciousness disturbances in megalencephalic leukoencephalopathy with subcortical cysts. Neuropediatrics. 34:211–214CrossRefPubMedGoogle Scholar
  22. 22.
    Mejaski-Bosnjak V, Besenski N, Brockmann K, Pouwels PJ, Frahm J, Hanefeld FA (1997) Cystic leukoencephalopathy in a megalencephalic child: clinical and magnetic resonance imaging/magnetic resonance spectroscopy findings. Pediatr Neurol 16:347–350CrossRefPubMedGoogle Scholar
  23. 23.
    Lanciotti A, Brignone MS, Visentin S, De Nuccio C, Catacuzzeno L, Mallozzi C, Petrini S, Caramia M et al (2016) Megalencephalic leukoencephalopathy with subcortical cysts protein-1 regulates epidermal growth factor receptor signaling in astrocytes. Hum Mol Genet 25:1543–1558CrossRefPubMedGoogle Scholar
  24. 24.
    Gao WL, Tian F, Zhang SQ, Zhang H, Yin ZS (2014) Epidermal growth factor increases the expression of Nestin in rat reactive astrocytes through the Ras-Raf-ERK pathway. Neurosci Lett 562:54-59Google Scholar
  25. 25.
    Burda JE, Sofroniew MV (2014) Reactive gliosis and the multicellular response to CNS damage and disease. Neuron. 81:229–248CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Wei T, Yi M, Gu W, Hou L, Lu Q, Yu Z, Chen H (2017) The Potassium Channel KCa3.1 represents a valid pharmacological target for Astrogliosis-induced neuronal impairment in a mouse model of Alzheimer's disease. Front Pharmacol 7:528CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Yi M, Wei T, Wang Y, Lu Q, Chen G, Gao X, Geller HM, Chen H et al (2017) The potassium channel KCa3.1 constitutes a pharmacological target for astrogliosis associated with ischemia stroke. J Neuroinflammation 14:203–017-0973-8CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Elorza-Vidal X, Sirisi S, Gaitan-Penas H, Perez-Rius C, Alonso-Gardon M, Armand-Ugon M, Lanciotti A, Brignone MS et al (2018) GlialCAM/MLC1 modulates LRRC8/VRAC currents in an indirect manner: implications for megalencephalic leukoencephalopathy. Neurobiol Dis 119:88–99CrossRefPubMedGoogle Scholar
  29. 29.
    Petrini S, Minnone G, Coccetti M, Frank C, Aiello C, Cutarelli A, Ambrosini E, Lanciotti A et al (2013) Monocytes and macrophages as biomarkers for the diagnosis of megalencephalic leukoencephalopathy with subcortical cysts. Mol Cell Neurosci 56:307–321CrossRefPubMedGoogle Scholar
  30. 30.
    Agresti C, Aloisi F, Levi G (1991) Heterotypic and homotypic cellular interactions influencing the growth and differentiation of bipotential oligodendrocyte-type-2 astrocyte progenitors in culture. Dev Biol 144:16–29CrossRefPubMedGoogle Scholar
  31. 31.
    Lanciotti A, Brignone MS, Molinari P, Visentin S, De Nuccio C, Macchia G, Aiello C, Bertini E et al (2012) Megalencephalic leukoencephalopathy with subcortical cysts protein 1 functionally cooperates with the TRPV4 cation channel to activate the response of astrocytes to osmotic stress: dysregulation by pathological mutations. Hum Mol Genet 21:2166–2180CrossRefPubMedGoogle Scholar
  32. 32.
    Lanciotti A, Brignone MS, Camerini S, Serafini B, Macchia G, Raggi C, Molinari P, Crescenzi M et al (2010) MLC1 trafficking and membrane expression in astrocytes: role of caveolin-1 and phosphorylation. Neurobiol Dis 37:581–595CrossRefPubMedGoogle Scholar
  33. 33.
    Brignone MS, Lanciotti A, Visentin S, De Nuccio C, Molinari P, Camerini S, Diociaiuti M, Petrini S et al (2014) Megalencephalic leukoencephalopathy with subcortical cysts protein-1 modulates endosomal pH and protein trafficking in astrocytes: relevance to MLC disease pathogenesis. Neurobiol Dis 66:1–18CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Ambrosini E, Serafini B, Lanciotti A, Tosini F, Scialpi F, Psaila R, Raggi C, Di Girolamo F et al (2008) Biochemical characterization of MLC1 protein in astrocytes and its association with the dystrophin-glycoprotein complex. Mol Cell Neurosci 37:480–493CrossRefPubMedGoogle Scholar
  35. 35.
    Eleuteri C, Olla S, Veroni C, Umeton R, Mechelli R, Romano S, Buscarinu MC, Ferrari F et al (2017) A staged screening of registered drugs highlights remyelinating drug candidates for clinical trials. Sci Rep 7:45780CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Lassmann H (2018) Multiple sclerosis pathology. Cold Spring Harb Perspect Med 8.  https://doi.org/10.1101/cshperspect.a028936
  37. 37.
    Stadelmann C (2011) Multiple sclerosis as a neurodegenerative disease: pathology, mechanisms and therapeutic implications. Curr Opin Neurol 24:224–229CrossRefPubMedGoogle Scholar
  38. 38.
    Boor PK, de Groot K, Waisfisz Q, Kamphorst W, Oudejans CB, Powers JM, Pronk JC, Scheper GC et al (2005) MLC1: a novel protein in distal astroglial processes. J Neuropathol Exp Neurol 64:412–419CrossRefPubMedGoogle Scholar
  39. 39.
    Stephenson J, Nutma E, van der Valk P, Amor S (2018) Inflammation in CNS neurodegenerative diseases. Immunology. 154:204–219CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Zenaro E, Piacentino G, Constantin G (2017) The blood-brain barrier in Alzheimer's disease. Neurobiol Dis 107:41–56CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Iwasaki Y, Mori K, Ito M, Tatsumi S, Mimuro M, Yoshida M (2013) An autopsied case of progressive supranuclear palsy presenting with cerebellar ataxia and severe cerebellar involvement. Neuropathology. 33:561–567PubMedGoogle Scholar
  42. 42.
    Lewicki H, Tishon A, Homann D, Mazarguil H, Laval F, Asensio VC, Campbell IL, DeArmond S et al (2003) T cells infiltrate the brain in murine and human transmissible spongiform encephalopathies. J Virol 77:3799–3808CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Verkhratsky A, Zorec R, Rodriguez JJ, Parpura V (2016) Astroglia dynamics in ageing and Alzheimer's disease. Curr Opin Pharmacol 26:74–79CrossRefPubMedGoogle Scholar
  44. 44.
    Gomez-Arboledas A, Davila JC, Sanchez-Mejias E, Navarro V, Nunez-Diaz C, Sanchez-Varo R, Sanchez-Mico MV, Trujillo-Estrada L et al (2018) Phagocytic clearance of presynaptic dystrophies by reactive astrocytes in Alzheimer's disease. Glia. 66:637–653CrossRefPubMedGoogle Scholar
  45. 45.
    Van Everbroeck B, Dewulf E, Pals P, Lubke U, Martin JJ, Cras P (2002) The role of cytokines, astrocytes, microglia and apoptosis in Creutzfeldt-Jakob disease. Neurobiol Aging 23:59–64CrossRefPubMedGoogle Scholar
  46. 46.
    Rubio-Perez JM, Morillas-Ruiz JM (2012) A review: inflammatory process in Alzheimer's disease, role of cytokines. ScientificWorldJournal. 2012:756357CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Lucas SM, Rothwell NJ, Gibson RM (2006) The role of inflammation in CNS injury and disease. Br J Pharmacol 147(Suppl 1):S232–S240PubMedPubMedCentralGoogle Scholar
  48. 48.
    Parker LC, Luheshi GN, Rothwell NJ, Pinteaux E (2002) IL-1 beta signalling in glial cells in wildtype and IL-1RI deficient mice. Br J Pharmacol 136:312–320CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Nadjar A, Combe C, Busquet P, Dantzer R, Parnet P (2005) Signaling pathways of interleukin-1 actions in the brain: anatomical distribution of phospho-ERK1/2 in the brain of rat treated systemically with interleukin-1beta. Neuroscience. 134:921–932CrossRefPubMedGoogle Scholar
  50. 50.
    Meini A, Sticozzi C, Massai L, Palmi M (2008) A nitric oxide/Ca(2+)/calmodulin/ERK1/2 mitogen-activated protein kinase pathway is involved in the mitogenic effect of IL-1beta in human astrocytoma cells. Br J Pharmacol 153:1706–1717CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Summers L, Kangwantas K, Nguyen L, Kielty C, Pinteaux E (2010) Adhesion to the extracellular matrix is required for interleukin-1 beta actions leading to reactive phenotype in rat astrocytes. Mol Cell Neurosci 44:272–281CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Marcus JS, Karackattu SL, Fleegal MA, Sumners C (2003) Cytokine-stimulated inducible nitric oxide synthase expression in astroglia: role of Erk mitogen-activated protein kinase and NF-kappaB. Glia. 41:152–160CrossRefPubMedGoogle Scholar
  53. 53.
    Wang T, Yuan W, Liu Y, Zhang Y, Wang Z, Zhou X, Ning G, Zhang L et al (2015) The role of the JAK-STAT pathway in neural stem cells, neural progenitor cells and reactive astrocytes after spinal cord injury. Biomed Rep 3:141–146CrossRefPubMedGoogle Scholar
  54. 54.
    Ben Haim L, Ceyzeriat K, Carrillo-de Sauvage MA, Aubry F, Auregan G, Guillermier M, Ruiz M, Petit F et al (2015) The JAK/STAT3 pathway is a common inducer of astrocyte reactivity in Alzheimer's and Huntington's diseases. J Neurosci 35:2817–2829CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Konnikova L, Kotecki M, Kruger MM, Cochran BH (2003) Knockdown of STAT3 expression by RNAi induces apoptosis in astrocytoma cells. BMC Cancer 3:23–2407-3-23CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Lindemann C, Hackmann O, Delic S, Schmidt N, Reifenberger G, Riemenschneider MJ (2011) SOCS3 promoter methylation is mutually exclusive to EGFR amplification in gliomas and promotes glioma cell invasion through STAT3 and FAK activation. Acta Neuropathol 122:241–251CrossRefPubMedGoogle Scholar
  57. 57.
    Barateiro A, Afonso V, Santos G, Cerqueira JJ, Brites D, van Horssen J, Fernandes A (2016) S100B as a potential biomarker and therapeutic target in multiple sclerosis. Mol Neurobiol 53:3976–3991CrossRefPubMedGoogle Scholar
  58. 58.
    Birgbauer E, Rao TS, Webb M (2004) Lysolecithin induces demyelination in vitro in a cerebellar slice culture system. J Neurosci Res 78:157–166CrossRefPubMedGoogle Scholar
  59. 59.
    Brignone MS, Lanciotti A, Macioce P, Macchia G, Gaetani M, Aloisi F, Petrucci TC, Ambrosini E (2011) The beta1 subunit of the Na,K-ATPase pump interacts with megalencephalic leucoencephalopathy with subcortical cysts protein 1 (MLC1) in brain astrocytes: New insights into MLC pathogenesis. Hum Mol Genet 20:90–103CrossRefPubMedGoogle Scholar
  60. 60.
    Sofroniew MV (2015) Astrocyte barriers to neurotoxic inflammation. Nat Rev Neurosci 16:249–263CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Griffin WS (2006) Inflammation and neurodegenerative diseases. Am J Clin Nutr 83:470S–474SCrossRefPubMedGoogle Scholar
  62. 62.
    Griffin WS, Liu L, Li Y, Mrak RE, Barger SW (2006) Interleukin-1 mediates Alzheimer and Lewy body pathologies. J Neuroinflammation 3:5–2094-3-5CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Rezaie P, Lantos PL (2001) Microglia and the pathogenesis of spongiform encephalopathies. Brain Res Brain Res Rev 35:55–72CrossRefPubMedGoogle Scholar
  64. 64.
    Amor S, Peferoen LA, Vogel DY, Breur M, van der Valk P, Baker D, van Noort JM (2014) Inflammation in neurodegenerative diseases--an update. Immunology. 142:151–166CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Rozemuller AJ, Jansen C, Carrano A, van Haastert ES, Hondius D, van der Vies SM, Hoozemans JJ (2012) Neuroinflammation and common mechanism in Alzheimer's disease and prion amyloidosis: amyloid-associated proteins, neuroinflammation and neurofibrillary degeneration. Neurodegener Dis 10:301–304CrossRefPubMedGoogle Scholar
  66. 66.
    Heneka MT (2017) Inflammasome activation and innate immunity in Alzheimer's disease. Brain Pathol 27:220–222CrossRefPubMedGoogle Scholar
  67. 67.
    Guillot-Sestier MV, Town T (2017) Let's make microglia great again in neurodegenerative disorders. J Neural Transm (Vienna)Google Scholar
  68. 68.
    Stoeck K, Schmitz M, Ebert E, Schmidt C, Zerr I (2014) Immune responses in rapidly progressive dementia: a comparative study of neuroinflammatory markers in Creutzfeldt-Jakob disease, Alzheimer's disease and multiple sclerosis. J Neuroinflammation 11:170–014-0170-yCrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Aguzzi A, Liu Y (2017) A role for astroglia in prion diseases. J Exp Med 214:3477–3479CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Avila-Munoz E, Arias C (2014) When astrocytes become harmful: functional and inflammatory responses that contribute to Alzheimer's disease. Ageing Res Rev 18:29–40CrossRefPubMedGoogle Scholar
  71. 71.
    Alam Q, Alam MZ, Mushtaq G, Damanhouri GA, Rasool M, Kamal MA, Haque A (2016) Inflammatory process in Alzheimer's and Parkinson's diseases: Central role of cytokines. Curr Pharm Des 22:541–548CrossRefPubMedGoogle Scholar
  72. 72.
    Frost GR , Li YM (2017) The role of astrocytes in amyloid production and Alzheimer's disease. Open Biol 7(12)Google Scholar
  73. 73.
    Taib T, Leconte C, Van Steenwinckel J, Cho AH, Palmier B, Torsello E, Lai Kuen R, Onyeomah S et al (2017) Neuroinflammation, myelin and behavior: temporal patterns following mild traumatic brain injury in mice. PLoS One 12:e0184811CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Zetterstrom M, Sundgren-Andersson AK, Ostlund P, Bartfai T (1998) Delineation of the proinflammatory cytokine cascade in fever induction. Ann N Y Acad Sci 856:48–52CrossRefPubMedGoogle Scholar
  75. 75.
    Sun M, Brady RD, Wright DK, Kim HA, Zhang SR, Sobey CG, Johnstone MR, O'Brien TJ et al (2017) Treatment with an interleukin-1 receptor antagonist mitigates neuroinflammation and brain damage after polytrauma. Brain Behav Immun 66:359–371CrossRefPubMedGoogle Scholar
  76. 76.
    Lu KT, Wang YW, Yang JT, Yang YL, Chen HI (2005) Effect of interleukin-1 on traumatic brain injury-induced damage to hippocampal neurons. J Neurotrauma 22:885–895CrossRefPubMedGoogle Scholar
  77. 77.
    Sticozzi C, Belmonte G, Meini A, Carbotti P, Grasso G, Palmi M (2013) IL-1beta induces GFAP expression in vitro and in vivo and protects neurons from traumatic injury-associated apoptosis in rat brain striatum via NFkappaB/Ca(2)(+)-calmodulin/ERK mitogen-activated protein kinase signaling pathway. Neuroscience. 252:367–383CrossRefPubMedGoogle Scholar
  78. 78.
    Fields J, Cisneros IE, Borgmann K, Ghorpade A (2013) Extracellular regulated kinase 1/2 signaling is a critical regulator of interleukin-1beta-mediated astrocyte tissue inhibitor of metalloproteinase-1 expression. PLoS One 8:e56891CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Cheng P, Alberts I, Li X (2013) The role of ERK1/2 in the regulation of proliferation and differentiation of astrocytes in developing brain. Int J Dev Neurosci 31:783–789CrossRefPubMedGoogle Scholar
  80. 80.
    Sun J, Nan G (2017) The extracellular signal-regulated kinase 1/2 pathway in neurological diseases: a potential therapeutic target (review). Int J Mol Med 39:1338–1346CrossRefPubMedPubMedCentralGoogle Scholar
  81. 81.
    Rama Rao KV, Jayakumar AR, Tong X, Alvarez VM, Norenberg MD (2010) Marked potentiation of cell swelling by cytokines in ammonia-sensitized cultured astrocytes. J Neuroinflammation 7:66–2094-7-66CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Mori T, Wang X, Aoki T, Lo EH (2002) Downregulation of matrix metalloproteinase-9 and attenuation of edema via inhibition of ERK mitogen activated protein kinase in traumatic brain injury. J Neurotrauma 19:1411–1419CrossRefPubMedGoogle Scholar
  83. 83.
    Hui H, Rao W, Zhang L, Xie Z, Peng C, Su N, Wang K, Wang L et al (2016) Inhibition of Na(+)-K(+)-2Cl(−) cotransporter-1 attenuates traumatic brain injury-induced neuronal apoptosis via regulation of Erk signaling. Neurochem Int 94:23–31CrossRefPubMedGoogle Scholar
  84. 84.
    Yang Z, Fan R, Sun P, Cui H, Peng W, Luo J, Zhang C, Xiong X et al (2018) Rhubarb attenuates cerebral edema via inhibition of the extracellular signal-regulated kinase pathway following traumatic brain injury in rats. Pharmacogn Mag 14:134–139CrossRefPubMedPubMedCentralGoogle Scholar
  85. 85.
    van der Knaap MS, Boor I, Estevez R (2012) Megalencephalic leukoencephalopathy with subcortical cysts: chronic white matter oedema due to a defect in brain ion and water homoeostasis. Lancet Neurol 11:973–985CrossRefPubMedGoogle Scholar
  86. 86.
    Liu S, Zhu S, Zou Y, Wang T, Fu X (2015) Knockdown of IL-1beta improves hypoxia-ischemia brain associated with IL-6 up-regulation in cell and animal models. Mol Neurobiol 51:743–752CrossRefPubMedGoogle Scholar
  87. 87.
    Eng LF, Ghirnikar RS (1994) GFAP and astrogliosis. Brain Pathol 4:229–237CrossRefPubMedGoogle Scholar
  88. 88.
    Ceyzeriat K, Abjean L, Carrillo-de Sauvage MA, Ben Haim L, Escartin C (2016) The complex STATes of astrocyte reactivity: how are they controlled by the JAK-STAT3 pathway? Neuroscience. 330:205–218CrossRefPubMedGoogle Scholar
  89. 89.
    Toutounchian JJ, McCarty JH (2017) Selective expression of eGFP in mouse perivascular astrocytes by modification of the Mlc1 gene using T2A-based ribosome skipping. Genesis. 55.  https://doi.org/10.1002/dvg.23071
  90. 90.
    Estevez R, Elorza-Vidal X, Gaitan-Penas H, Perez-Rius C, Armand-Ugon M, Alonso-Gardon M, Xicoy-Espaulella E, Sirisi S et al (2018) Megalencephalic leukoencephalopathy with subcortical cysts: a personal biochemical retrospective. Eur J Med Genet 61:50–60CrossRefPubMedGoogle Scholar
  91. 91.
    Sirisi S, Elorza-Vidal X, Arnedo T, Armand-Ugon M, Callejo G, Capdevila-Nortes X, Lopez-Hernandez T, Schulte U et al (2017) Depolarization causes the formation of a ternary complex between GlialCAM, MLC1 and ClC-2 in astrocytes: implications in megalencephalic leukoencephalopathy. Hum Mol Genet 26:2436–2450CrossRefPubMedGoogle Scholar
  92. 92.
    Dubey M, Brouwers E, Hamilton EMC, Stiedl O, Bugiani M, Koch H, Kole MHP, Boschert U et al (2018) Seizures and disturbed brain potassium dynamics in the leukodystrophy megalencephalic leukoencephalopathy with subcortical cysts. Ann Neurol 83:636–649CrossRefPubMedPubMedCentralGoogle Scholar
  93. 93.
    Tzour A, Leibovich H, Barkai O, Biala Y, Lev S, Yaari Y, Binshtok AM (2017) KV 7/M channels as targets for lipopolysaccharide-induced inflammatory neuronal hyperexcitability. J Physiol 595:713–738CrossRefPubMedGoogle Scholar
  94. 94.
    Neprasova H, Anderova M, Petrik D, Vargova L, Kubinova S, Chvatal A, Sykova E (2007) High extracellular K(+) evokes changes in voltage-dependent K(+) and Na (+) currents and volume regulation in astrocytes. Pflugers Arch 453:839–849CrossRefPubMedGoogle Scholar
  95. 95.
    Okazaki R, Doi T, Hayakawa K, Morioka K, Imamura O, Takishima K, Hamanoue M, Sawada Y et al (2016) The crucial role of Erk2 in demyelinating inflammation in the central nervous system. J Neuroinflammation 13:235–016-0690-8CrossRefPubMedPubMedCentralGoogle Scholar
  96. 96.
    Hamilton EMC, Tekturk P, Cialdella F, van Rappard DF, Wolf NI, Yalcinkaya C, Cetincelik U, Rajaee A et al (2018) Megalencephalic leukoencephalopathy with subcortical cysts: characterization of disease variants. Neurology. 90:e1395–e1403CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Maria Stefania Brignone
    • 1
  • Angela Lanciotti
    • 1
  • Barbara Serafini
    • 1
  • Cinzia Mallozzi
    • 1
  • Marco Sbriccoli
    • 1
  • Caterina Veroni
    • 1
  • Paola Molinari
    • 2
  • Xabier Elorza-Vidal
    • 3
  • Tamara Corinna Petrucci
    • 1
  • Raul Estévez
    • 3
    • 4
  • Elena Ambrosini
    • 1
    Email author
  1. 1.Department of NeuroscienceIstituto Superiore di SanitàRomeItaly
  2. 2.Department of FARVAIstituto Superiore di SanitàRomeItaly
  3. 3.Unitat de Fisiologia, Departamento de Ciències Fisiològiques, IDIBELL-Institute of NeurosciencesUniversitat de BarcelonaL’Hospitalet de LlobregatSpain
  4. 4.Centro de Investigación en Red de Enfermedades Raras (CIBERER), ISCIIIValencianaSpain

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