Journal of Neuroimmune Pharmacology

, Volume 7, Issue 4, pp 1002–1016 | Cite as

A Cannabigerol Quinone Alleviates Neuroinflammation in a Chronic Model of Multiple Sclerosis

  • Aitor G. Granja
  • Francisco Carrillo-Salinas
  • Alberto Pagani
  • María Gómez-Cañas
  • Roberto Negri
  • Carmen Navarrete
  • Miriam Mecha
  • Leyre Mestre
  • Bend L. Fiebich
  • Irene Cantarero
  • Marco A. Calzado
  • Maria L. Bellido
  • Javier Fernandez-Ruiz
  • Giovanni Appendino
  • Carmen Guaza
  • Eduardo MuñozEmail author


Phytocannabinoids like ∆9-tetrahydrocannabinol (THC) and cannabidiol (CBD) show a beneficial effect on neuroinflammatory and neurodegenerative processes through cell membrane cannabinoid receptor (CBr)-dependent and -independent mechanisms. Natural and synthetic cannabinoids also target the nuclear receptor peroxisome proliferator-activated receptor-gamma (PPARγ), an attractive molecular target for the treatment of neuroinflammation. As part of a study on the SAR of phytocannabinoids, we have investigated the effect of the oxidation modification in the resorcinol moiety of cannabigerol (CBG) on CB1, CB2 and PPARγ binding affinities, identifying cannabigerol quinone (VCE-003) as a potent anti-inflammatory agent. VCE-003 protected neuronal cells from excitotoxicity, activated PPARγ transcriptional activity and inhibited the release of pro-inflammatory mediators in LPS-stimulated microglial cells. Theiler’s murine encephalomyelitis virus (TMEV) model of multiple sclerosis (MS) was used to investigate the anti-inflammatory activity of this compound in vivo. Motor function performance was evaluated and the neuroinflammatory response and gene expression pattern in brain and spinal cord were studied by immunostaining and qRT-PCR. We found that VCE-003 ameliorated the symptoms associated to TMEV infection, decreased microglia reactivity and modulated the expression of genes involved in MS pathophysiology. These data lead us to consider VCE-003 to have high potential for drug development against MS and perhaps other neuroinflammatory diseases.


Cannabinoids Cannabigerol PPARγ Neuroinflammation Multiple sclerosis 







Experimental autoimmune encephalomyelitis


Forkhead box P3


Intercellular adhesion molecule 1


Induced Demyelinating Disease


Prostaglandin E2


Peroxisome proliferator-activated receptor






Theiler’s Murine Encephalomyelitis Virus


Very late antigen 4



This work was supported supported by the MINECO grants IPT-2011-0861-900000 (EM and CG), SAF2010-19292 (EM), SAF2010-17501 (CG), SAF2009-11847 (JFR), S2010/BMD-2308 (CG and JFR) and by RETICS RIS RD06/0006/0028 and REEM RD07/0060/0010. Finally, we thank Ms. Carmen Cabrero-Doncel for her assistance with the manuscript.

Conflict of interest

MLB, GA and EM have filed a PCT application “Cannabinoid quinone derivatives” (application number PCT-03494). All the other authors declare no conflict of interest.

Supplementary material

11481_2012_9399_MOESM1_ESM.doc (36 kb)
ESM 1 (DOC 36 kb)
11481_2012_9399_MOESM2_ESM.pptx (1.4 mb)
ESM 2 (PPTX 1409 kb)


  1. Appendino G, Gibbons S, Giana A, Pagani A, Grassi G, Stavri M, Smith E, Rahman MM (2008) Antibacterial cannabinoids from Cannabis sativa: a structure-activity study. J Nat Prod 71(8):1427–1430. doi: 10.1021/np8002673 PubMedCrossRefGoogle Scholar
  2. Arevalo-Martin A, Molina-Holgado E, Guaza C (2012) A CB(1)/CB(2) receptor agonist, WIN 55,212-2, exerts its therapeutic effect in a viral autoimmune model of multiple sclerosis by restoring self-tolerance to myelin. Neuropharmacology 63(3):385–393. doi: 10.1016/j.neuropharm.2012.04.012 PubMedCrossRefGoogle Scholar
  3. Bauer J, Sminia T, Wouterlood FG, Dijkstra CD (1994) Phagocytic activity of macrophages and microglial cells during the course of acute and chronic relapsing experimental autoimmune encephalomyelitis. J Neurosci Res 38(4):365–375. doi: 10.1002/jnr.490380402 PubMedCrossRefGoogle Scholar
  4. Ben-Baruch A, Xu L, Young PR, Bengali K, Oppenheim JJ, Wang JM (1995) Monocyte chemotactic protein-3 (MCP3) interacts with multiple leukocyte receptors. C-C CKR1, a receptor for macrophage inflammatory protein-1 alpha/Rantes, is also a functional receptor for MCP3. J Biol Chem 270(38):22123–22128. doi: 10.1074/jbc.270.38.22123 PubMedCrossRefGoogle Scholar
  5. Bensinger SJ, Tontonoz P (2008) Integration of metabolism and inflammation by lipid-activated nuclear receptors. Nature 454(7203):470–477. doi: 10.1038/nature07202 PubMedCrossRefGoogle Scholar
  6. Benveniste EN (1997) Cytokines: influence on glial cell gene expression and function. Chem Immunol 69:31–75. doi: 10.1159/000058653 PubMedCrossRefGoogle Scholar
  7. Cascio MG, Gauson LA, Stevenson LA, Ross RA, Pertwee RG (2010) Evidence that the plant cannabinoid cannabigerol is a highly potent alpha2-adrenoceptor agonist and moderately potent 5HT1A receptor antagonist. Br J Pharmacol 159(1):129–141. doi: 10.1111/j.1476-5381.2009.00515.x PubMedCrossRefGoogle Scholar
  8. Cole KE, Strick CA, Paradis TJ, Ogborne KT, Loetscher M, Gladue RP, Lin W, Boyd JG, Moser B, Wood DE, Sahagan BG, Neote K (1998) Interferon-inducible T cell alpha chemoattractant (I-TAC): a novel non-ELR CXC chemokine with potent activity on activated T cells through selective high affinity binding to CXCR3. J Exp Med 187(12):2009–2021. doi: 10.1084/jem.187.12.2009 PubMedCrossRefGoogle Scholar
  9. Cumella J, Hernandez-Folgado L, Giron R, Sanchez E, Morales P, Hurst DP, Gomez-Canas M, Gomez-Ruiz M, Pinto DC, Goya P, Reggio PH, Martin MI, Fernandez-Ruiz J, Silva AM, Jagerovic N (2012) Chromenopyrazoles: non-psychoactive and selective CB(1) cannabinoid agonists with peripheral antinociceptive properties. Chem Med Chem 7(3):452–463. doi: 10.1002/cmdc.201100568, 536PubMedGoogle Scholar
  10. de Oliveira AC, Candelario-Jalil E, Langbein J, Wendeburg L, Bhatia HS, Schlachetzki JC, Biber K, Fiebich BL (2012) Pharmacological inhibition of Akt and downstream pathways modulates the expression of COX-2 and mPGES-1 in activated microglia. J Neuroinflammation 9:2. doi: 10.1186/1742-2094-9-2 PubMedCrossRefGoogle Scholar
  11. De Petrocellis L, Vellani V, Schiano-Moriello A, Marini P, Magherini PC, Orlando P, Di Marzo V (2008) Plant-derived cannabinoids modulate the activity of transient receptor potential channels of ankyrin type-1 and melastatin type-8. J Pharmacol Exp Ther 325(3):1007–1015. doi: 10.1124/jpet.107.134809 PubMedCrossRefGoogle Scholar
  12. De Petrocellis L, Ligresti A, Moriello AS, Allara M, Bisogno T, Petrosino S, Stott CG, Di Marzo V (2011) Effects of cannabinoids and cannabinoid-enriched Cannabis extracts on TRP channels and endocannabinoid metabolic enzymes. Br J Pharmacol 163(7):1479–1494. doi: 10.1111/j.1476-5381.2010.01166.x PubMedCrossRefGoogle Scholar
  13. Elices MJ, Osborn L, Takada Y, Crouse C, Luhowskyj S, Hemler ME, Lobb RR (1990) VCAM-1 on activated endothelium interacts with the leukocyte integrin VLA-4 at a site distinct from the VLA-4/fibronectin binding site. Cell 60(4):577–584. doi: 0092-8674(90)90661-W PubMedCrossRefGoogle Scholar
  14. Esposito G, Scuderi C, Valenza M, Togna GI, Latina V, De Filippis D, Cipriano M, Carratu MR, Iuvone T, Steardo L (2011) Cannabidiol reduces Abeta-induced neuroinflammation and promotes hippocampal neurogenesis through PPARgamma involvement. PLoS One 6(12):e28668. doi: 10.1371/journal.pone.0028668 PubMedCrossRefGoogle Scholar
  15. Evans R, Patzak I, Svensson L, De Filippo K, Jones K, McDowall A, Hogg N (2009) Integrins in immunity. J Cell Sci 122(Pt 2):215–225. doi: 10.1242/jcs.019117 PubMedCrossRefGoogle Scholar
  16. Feger U, Luther C, Poeschel S, Melms A, Tolosa E, Wiendl H (2007) Increased frequency of CD4+ CD25+ regulatory T cells in the cerebrospinal fluid but not in the blood of multiple sclerosis patients. Clin Exp Immunol 147(3):412–418. doi: 10.1111/j.1365-2249.2006.03271.x PubMedCrossRefGoogle Scholar
  17. Feinstein DL, Galea E, Gavrilyuk V, Brosnan CF, Whitacre CC, Dumitrescu-Ozimek L, Landreth GE, Pershadsingh HA, Weinberg G, Heneka MT (2002) Peroxisome proliferator-activated receptor-gamma agonists prevent experimental autoimmune encephalomyelitis. Ann Neurol 51(6):694–702. doi: 10.1002/ana.10206 PubMedCrossRefGoogle Scholar
  18. Franklin RJ, Ffrench-Constant C (2008) Remyelination in the CNS: from biology to therapy. Nat Rev Neurosci 9(11):839–855. doi: 10.1038/nrn2480 PubMedCrossRefGoogle Scholar
  19. Gao JL, Kuhns DB, Tiffany HL, McDermott D, Li X, Francke U, Murphy PM (1993) Structure and functional expression of the human macrophage inflammatory protein 1 alpha/RANTES receptor. J Exp Med 177(5):1421–1427. doi: 10.1084/jem.177.5.1421 PubMedCrossRefGoogle Scholar
  20. Glass CK, Saijo K, Winner B, Marchetto MC, Gage FH (2010) Mechanisms underlying inflammation in neurodegeneration. Cell 140(6):918–934. doi: 10.1016/j.cell.2010.02.016 PubMedCrossRefGoogle Scholar
  21. Gonzalez-Amaro R, Mittelbrunn M, Sanchez-Madrid F (2005) Therapeutic anti-integrin (alpha4 and alphaL) monoclonal antibodies: two-edged swords? Immunology 116(3):289–296. doi: 10.1111/j.1365-2567.2005.02225.x PubMedCrossRefGoogle Scholar
  22. Haist V, Ulrich R, Kalkuhl A, Deschl U, Baumgartner W (2012) Distinct spatio-temporal extracellular matrix accumulation within demyelinated spinal cord lesions in Theiler’s murine encephalomyelitis. Brain Pathol 22(2):188–204. doi: 10.1111/j.1750-3639.2011.00518.x PubMedCrossRefGoogle Scholar
  23. Hao GH, Niu XL, Gao DF, Wei J, Wang NP (2008) Agonists at PPAR-gamma suppress angiotensin II-induced production of plasminogen activator inhibitor-1 and extracellular matrix in rat cardiac fibroblasts. Br J Pharmacol 153(7):1409–1419. doi: 10.1038/bjp.2008.21 PubMedCrossRefGoogle Scholar
  24. Hauser SL, Oksenberg JR (2006) The neurobiology of multiple sclerosis: genes, inflammation, and neurodegeneration. Neuron 52(1):61–76. doi: 10.1016/j.neuron.2006.09.011 PubMedCrossRefGoogle Scholar
  25. Hill AJ, Williams CM, Whalley BJ, Stephens GJ (2011) Phytocannabinoids as novel therapeutic agents in CNS disorders. Pharmacol Ther 133(1):79–97. doi: 10.1016/j.pharmthera.2011.09.002 PubMedCrossRefGoogle Scholar
  26. Hori S, Nomura T, Sakaguchi S (2003) Control of regulatory T cell development by the transcription factor Foxp3. Science 299(5609):1057–1061. doi: 10.1126/science.1079490 PubMedCrossRefGoogle Scholar
  27. Howlett AC, Barth F, Bonner TI, Cabral G, Casellas P, Devane WA, Felder CC, Herkenham M, Mackie K, Martin BR, Mechoulam R, Pertwee RG (2002) International Union of Pharmacology. XXVII. Classification of cannabinoid receptors. Pharmacol Rev 54(2):161–202. doi: 10.1124/pr.54.2.161 PubMedCrossRefGoogle Scholar
  28. Infante-Duarte C, Waiczies S, Wuerfel J, Zipp F (2008) New developments in understanding and treating neuroinflammation. J Mol Med (Berl) 86(9):975–985. doi: 10.1007/s00109-007-0292-0 CrossRefGoogle Scholar
  29. Inoue A, Koh CS, Yamazaki M, Ichikawa M, Isobe M, Ishihara Y, Yagita H, Kim BS (1997) Anti-adhesion molecule therapy in Theiler’s murine encephalomyelitis virus-induced demyelinating disease. Int Immunol 9(12):1837–1847. doi: 10.1093/intimm/9.12.1837 PubMedCrossRefGoogle Scholar
  30. Jiang C, Ting AT, Seed B (1998) PPAR-gamma agonists inhibit production of monocyte inflammatory cytokines. Nature 391(6662):82–86. doi: 10.1038/34184 PubMedCrossRefGoogle Scholar
  31. Kim BS, Palma JP, Kwon D, Fuller AC (2005) Innate immune response induced by Theiler’s murine encephalomyelitis virus infection. Immunol Res 31(1):1–12. doi: 10.1385/IR:31:1:01 PubMedCrossRefGoogle Scholar
  32. Kohm AP, Carpentier PA, Anger HA, Miller SD (2002) Cutting edge: CD4 + CD25+ regulatory T cells suppress antigen-specific autoreactive immune responses and central nervous system inflammation during active experimental autoimmune encephalomyelitis. J Immunol 169(9):4712–4716PubMedGoogle Scholar
  33. Kutzelnigg A, Lucchinetti CF, Stadelmann C, Bruck W, Rauschka H, Bergmann M, Schmidbauer M, Parisi JE, Lassmann H (2005) Cortical demyelination and diffuse white matter injury in multiple sclerosis. Brain 128(Pt 11):2705–2712. doi: 10.1093/brain/awh641 PubMedCrossRefGoogle Scholar
  34. Lee JM, Calkins MJ, Chan K, Kan YW, Johnson JA (2003) Identification of the NF-E2-related factor-2-dependent genes conferring protection against oxidative stress in primary cortical astrocytes using oligonucleotide microarray analysis. J Biol Chem 278(14):12029–12038. doi: 10.1074/jbc.M211558200 PubMedCrossRefGoogle Scholar
  35. Lehmann JM, Moore LB, Smith-Oliver TA, Wilkison WO, Willson TM, Kliewer SA (1995) An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor gamma (PPAR gamma). J Biol Chem 270(22):12953–12956. doi: 10.1074/jbc.270.22.12953 PubMedCrossRefGoogle Scholar
  36. Li Y, Maher P, Schubert D (1997) Requirement for cGMP in nerve cell death caused by glutathione depletion. J Cell Biol 139(5):1317–1324. doi: 10.1083/jcb.139.5.1317 PubMedCrossRefGoogle Scholar
  37. Li B, Jeong GS, Kang DG, Lee HS, Kim YC (2009) Cytoprotective effects of lindenenyl acetate isolated from Lindera strychnifolia on mouse hippocampal HT22 cells. Eur J Pharmacol 614(1–3):58–65. doi: 10.1016/j.ejphar.2009.04.056 PubMedCrossRefGoogle Scholar
  38. Liu J, Li H, Burstein SH, Zurier RB, Chen JD (2003) Activation and binding of peroxisome proliferator-activated receptor gamma by synthetic cannabinoid ajulemic acid. Mol Pharmacol 63(5):983–992. doi: 10.1124/mol.63.5.983 PubMedCrossRefGoogle Scholar
  39. Luster AD (1998) Chemokines–chemotactic cytokines that mediate inflammation. N Engl J Med 338(7):436–445. doi: 10.1056/NEJM199802123380706 PubMedCrossRefGoogle Scholar
  40. McFarland HF, Martin R (2007) Multiple sclerosis: a complicated picture of autoimmunity. Nat Immunol 8(9):913–919. doi: 10.1038/ni1507 PubMedCrossRefGoogle Scholar
  41. Mechoulam R, Gaoni Y (1967) The absolute configuration of delta-1-tetrahydrocannabinol, the major active constituent of hashish. Tetrahedron Lett 12:1109–1111. doi: 10.1016/S0040-4039(00)90646-4 PubMedCrossRefGoogle Scholar
  42. Mestre L, Docagne F, Correa F, Loria F, Hernangomez M, Borrell J, Guaza C (2009) A cannabinoid agonist interferes with the progression of a chronic model of multiple sclerosis by downregulating adhesion molecules. Mol Cell Neurosci 40(2):258–266. doi: 10.1016/j.mcn.2008.10.015 PubMedCrossRefGoogle Scholar
  43. Miller DH, Khan OA, Sheremata WA, Blumhardt LD, Rice GP, Libonati MA, Willmer-Hulme AJ, Dalton CM, Miszkiel KA, O’Connor PW (2003) A controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 348(1):15–23. doi: 10.1056/NEJMoa020696 PubMedCrossRefGoogle Scholar
  44. Molina-Holgado E, Vela JM, Arevalo-Martin A, Guaza C (2001) LPS/IFN-gamma cytotoxicity in oligodendroglial cells: role of nitric oxide and protection by the anti-inflammatory cytokine IL-10. Eur J Neurosci 13(3):493–502. doi: ejn1412 PubMedCrossRefGoogle Scholar
  45. Moreno S, Farioli-Vecchioli S, Ceru MP (2004) Immunolocalization of peroxisome proliferator-activated receptors and retinoid X receptors in the adult rat CNS. Neuroscience 123(1):131–145. doi: S0306452203006377 PubMedCrossRefGoogle Scholar
  46. Mrak RE, Landreth GE (2004) PPARgamma, neuroinflammation, and disease. J Neuroinflammation 1(1):5. doi: 10.1186/1742-2094-1-5 PubMedCrossRefGoogle Scholar
  47. Murray PD, Krivacic K, Chernosky A, Wei T, Ransohoff RM, Rodriguez M (2000) Biphasic and regionally-restricted chemokine expression in the central nervous system in the Theiler’s virus model of multiple sclerosis. J Neurovirol 6(Suppl 1):S44–S52. doi: PMID-10871765 PubMedGoogle Scholar
  48. Niino M, Iwabuchi K, Kikuchi S, Ato M, Morohashi T, Ogata A, Tashiro K, Onoe K (2001) Amelioration of experimental autoimmune encephalomyelitis in C57BL/6 mice by an agonist of peroxisome proliferator-activated receptor-gamma. J Neuroimmunol 116(1):40–48. doi: S0165-5728(01)00285-5 PubMedCrossRefGoogle Scholar
  49. O’Sullivan SE (2007) Cannabinoids go nuclear: evidence for activation of peroxisome proliferator-activated receptors. Br J Pharmacol 152(5):576–582. doi: 10.1038/sj.bjp. 0707423 PubMedCrossRefGoogle Scholar
  50. O’Sullivan SE, Tarling EJ, Bennett AJ, Kendall DA, Randall MD (2005) Novel time-dependent vascular actions of Delta9-tetrahydrocannabinol mediated by peroxisome proliferator-activated receptor gamma. Biochem Biophys Res Commun 337(3):824–831. doi: 10.1016/j.bbrc.2005.09.121 PubMedCrossRefGoogle Scholar
  51. O’Sullivan SE, Kendall DA, Randall MD (2009) Time-dependent vascular effects of endocannabinoids mediated by Peroxisome Proliferator-Activated Receptor Gamma (PPARgamma). PPAR Res 2009:425289. doi: 10.1155/2009/425289 PubMedGoogle Scholar
  52. Perry VH, Cunningham C, Holmes C (2007) Systemic infections and inflammation affect chronic neurodegeneration. Nat Rev Immunol 7(2):161–167. doi: 10.1038/nri2015 PubMedCrossRefGoogle Scholar
  53. Pershadsingh HA, Heneka MT, Saini R, Amin NM, Broeske DJ, Feinstein DL (2004) Effect of pioglitazone treatment in a patient with secondary multiple sclerosis. J Neuroinflammation 1(1):3. doi: 10.1186/1742-2094-1-3 PubMedCrossRefGoogle Scholar
  54. Qin S, Rottman JB, Myers P, Kassam N, Weinblatt M, Loetscher M, Koch AE, Moser B, Mackay CR (1998) The chemokine receptors CXCR3 and CCR5 mark subsets of T cells associated with certain inflammatory reactions. J Clin Invest 101(4):746–754. doi: 10.1172/JCI1422 PubMedCrossRefGoogle Scholar
  55. Rose K, Christine CW, Choi DW (1990) Magnesium removal induces paroxysmal neuronal firing and NMDA receptor-mediated neuronal degeneration in cortical cultures. Neurosci Lett 115(2–3):313–317. doi: 10.1016/0304-3940(90)90474-N PubMedCrossRefGoogle Scholar
  56. Saijo K, Winner B, Carson CT, Collier JG, Boyer L, Rosenfeld MG, Gage FH, Glass CK (2009) A Nurr1/CoREST pathway in microglia and astrocytes protects dopaminergic neurons from inflammation-induced death. Cell 137(1):47–59. doi: 10.1016/j.cell.2009.01.038 PubMedCrossRefGoogle Scholar
  57. Samson M, Labbe O, Mollereau C, Vassart G, Parmentier M (1996) Molecular cloning and functional expression of a new human CC-chemokine receptor gene. Biochemistry 35(11):3362–3367. doi: 10.1021/bi952950g PubMedCrossRefGoogle Scholar
  58. Sarafi MN, Garcia-Zepeda EA, MacLean JA, Charo IF, Luster AD (1997) Murine monocyte chemoattractant protein (MCP)-5: a novel CC chemokine that is a structural and functional homologue of human MCP-1. J Exp Med 185(1):99–109. doi: 10.1084/jem.185.1.99 PubMedCrossRefGoogle Scholar
  59. Sobel RA, Mitchell ME (1989) Fibronectin in multiple sclerosis lesions. Am J Pathol 135(1):161–168PubMedGoogle Scholar
  60. Taams LS, Vukmanovic-Stejic M, Smith J, Dunne PJ, Fletcher JM, Plunkett FJ, Ebeling SB, Lombardi G, Rustin MH, Bijlsma JW, Lafeber FP, Salmon M, Akbar AN (2002) Antigen-specific T cell suppression by human CD4 + CD25+ regulatory T cells. Eur J Immunol 32(6):1621–1630. doi: 10.1002/1521-4141(200206)32:6<1621::AID-IMMU1621>3.0.CO;2-Q PubMedCrossRefGoogle Scholar
  61. Tsunoda I, Fujinami RS (2009) Neuropathogenesis of Theiler’s murine encephalomyelitis virus infection, an animal model for multiple sclerosis. J Neuroimmune Pharmacol 5(3):355–369. doi: 10.1007/s11481-009-9179-x PubMedCrossRefGoogle Scholar
  62. Tubaro A, Giangaspero A, Sosa S, Negri R, Grassi G, Casano S, Della Loggia R, Appendino G (2010) Comparative topical anti-inflammatory activity of cannabinoids and cannabivarins. Fitoterapia 81(7):816–819. doi: 10.1016/j.fitote.2010.04.009 PubMedCrossRefGoogle Scholar
  63. Wang N, Verna L, Chen NG, Chen J, Li H, Forman BM, Stemerman MB (2002) Constitutive activation of peroxisome proliferator-activated receptor-gamma suppresses pro-inflammatory adhesion molecules in human vascular endothelial cells. J Biol Chem 277(37):34176–34181. doi: 10.1074/jbc.M203436200 PubMedCrossRefGoogle Scholar
  64. Yednock TA, Cannon C, Fritz LC, Sanchez-Madrid F, Steinman L, Karin N (1992) Prevention of experimental autoimmune encephalomyelitis by antibodies against alpha 4 beta 1 integrin. Nature 356(6364):63–66. doi: 10.1038/356063a0 PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Aitor G. Granja
    • 1
  • Francisco Carrillo-Salinas
    • 2
  • Alberto Pagani
    • 3
  • María Gómez-Cañas
    • 4
  • Roberto Negri
    • 3
  • Carmen Navarrete
    • 1
  • Miriam Mecha
    • 2
  • Leyre Mestre
    • 2
  • Bend L. Fiebich
    • 5
    • 6
  • Irene Cantarero
    • 7
  • Marco A. Calzado
    • 7
  • Maria L. Bellido
    • 1
  • Javier Fernandez-Ruiz
    • 4
  • Giovanni Appendino
    • 3
  • Carmen Guaza
    • 2
  • Eduardo Muñoz
    • 7
    Email author
  1. 1.Vivacell Biotechnology España S.L. Parque Científico Tecnológico Rabanales 21CórdobaSpain
  2. 2.Instituto CajalCSICMadridSpain
  3. 3.Dipartimento di Scienze FarmaceuticheUniversità del Piemonte OrientaleNovaraItaly
  4. 4.Departamento de Bioquímica y Biología Molecular, Instituto Universitario de Investigación en Neuroquímica, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Facultad de MedicinaUniversidad ComplutenseMadridSpain
  5. 5.Neurochemistry Research Group, Department of PsychiatryUniversity of Freiburg Medical SchoolFreiburgGermany
  6. 6.VivaCell Biotechnology GmbHDenzlingenGermany
  7. 7.Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Departamento de Biología Celular, Fisiología e InmunologíaUniversidad de CórdobaCórdobaSpain

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