title: Comparative Neuroregenerative Effects of C-Phycocyanin and IFN-Beta in a Model of Multiple Sclerosis in Mice.
abstract: Multiple Sclerosis (MS) therapies approved so far are unable to effectively reverse the chronic phase of the disease or improve the remyelination process. Here our aim is to evaluate the effects of C-Phycocyanin (C-Pc), a biliprotein from Spirulina platensis with anti-oxidant, anti-inflammatory and cytoprotective properties, in a chronic model of experimental autoimmune encephalomyelitis (EAE) in mice. C-Pc (2, 4 or 8 mg/kg i.p.) or IFN-beta (2000 IU, s.c.) was administered daily once a day or every other day, respectively, starting at disease onset, which differ among EAE mice between 11 and 15 days postinduction. Histological and immunohistochemistry (anti-Mac-3, anti-CD3 and anti-APP) assessments were performed in spinal cord in the postinduction time. Global gene expression in the brain was analyzed with the Illumina Mouse WG-6_V2 BeadChip microarray and the expression of particular genes, assessed by qPCR using the Fast SYBR Green RT-PCR Master Mix. Oxidative stress parameters (malondialdehyde, peroxidation potential, CAT/SOD ratio and GSH) were determined spectrophoto-metrically. Results showed that C-Pc ameliorates the clinical deterioration of animals, an effect that expresses the reduction of the inflammatory infiltrates invading the spinal cord tissue, the axonal preservation and the down-regulation of IL-17 expression in brain tissue and serum. C-Pc and IFN-beta improved the redox status in mice subjected to EAE, while microarray analysis showed that both treatments shared a common subset of differentially expressed genes, although they also differentially modulated another subset of genes. Specifically, C-Pc mainly modulated the expression of genes related to remyelination, gliogenesis and axon-glia processes. Taken together, our results indicate that C-Pc has significant therapeutic effects against EAE, mediated by the dynamic regulation of multiple biological processes.
authors.affiliation: Center for Genetic Engineering and Biotechnology (CIGB), Ave. 31 e/ 158 y 190, Cubanacán, Playa, PO Box 6162, Havana, 10 600, Cuba. giselle.penton@infomed.sld.cu.
authors.forename: Giselle
authors.initials: G
authors.lastname: Pentón-Rol
authors.affiliation: Center for Research and Biological Evaluations, Institute of Pharmacy and Food, University of Havana, PO. Box: 430, Havana, Cuba. nielsen15091984@gmail.com.
authors.forename: Nielsen
authors.initials: N
authors.lastname: Lagumersindez-Denis
authors.affiliation: Clinical Neuroimmunology and Division of Molecular Oncology Unit - Dibit, San Raffaele Scientific Institute, Milan, Italy. muzio.luca@hsr.it.
authors.forename: Luca
authors.initials: L
authors.lastname: Muzio
authors.affiliation: Clinical Neuroimmunology and Division of Molecular Oncology Unit - Dibit, San Raffaele Scientific Institute, Milan, Italy. bergami.alessandra@hsr.it.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bergami
authors.affiliation: Clinical Neuroimmunology and Division of Molecular Oncology Unit - Dibit, San Raffaele Scientific Institute, Milan, Italy. furlan.roberto@hsr.it.
authors.forename: Roberto
authors.initials: R
authors.lastname: Furlan
authors.affiliation: Center for Genetic Engineering and Biotechnology (CIGB), Ave. 31 e/ 158 y 190, Cubanacán, Playa, PO Box 6162, Havana, 10 600, Cuba. julio.fernandez@cigb.edu.cu.
authors.forename: Julio R
authors.initials: JR
authors.lastname: Fernández-Massó
authors.affiliation: Center for Genetic Engineering and Biotechnology (CIGB), Ave. 31 e/ 158 y 190, Cubanacán, Playa, PO Box 6162, Havana, 10 600, Cuba. marcelo.nazabal@cigb.edu.cu.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Nazabal-Galvez
authors.affiliation: Center for Genetic Engineering and Biotechnology (CIGB), Ave. 31 e/ 158 y 190, Cubanacán, Playa, PO Box 6162, Havana, 10 600, Cuba. alexey.llopiz@cigb.edu.cu.
authors.forename: Alexey
authors.initials: A
authors.lastname: Llópiz-Arzuaga
authors.affiliation: Center for Genetic Engineering and Biotechnology (CIGB), Ave. 31 e/ 158 y 190, Cubanacán, Playa, PO Box 6162, Havana, 10 600, Cuba. alberto.cintado@cigb.edu.cu.
authors.forename: Tania
authors.initials: T
authors.lastname: Herrera-Rolo
authors.affiliation: Clinical Neuroimmunology and Division of Molecular Oncology Unit - Dibit, San Raffaele Scientific Institute, Milan, Italy. velizrodriguez.tania@hsr.it.
authors.forename: Tania
authors.initials: T
authors.lastname: Veliz-Rodriguez
authors.affiliation: Istituto Clinico Humanitas (IRCCS), Rozzano, Italy. nadia.polentarutti@humanitasresearch.it.
authors.forename: Nadia
authors.initials: N
authors.lastname: Polentarutti
authors.affiliation: Center for Research and Biological Evaluations, Institute of Pharmacy and Food, University of Havana, PO. Box: 430, Havana, Cuba. jmarin@infomed.sld.cu.
authors.forename: Javier
authors.initials: J
authors.lastname: Marín-Prida
authors.affiliation: Center for Genetic Engineering and Biotechnology (CIGB), Ave. 31 e/ 158 y 190, Cubanacán, Playa, PO Box 6162, Havana, 10 600, Cuba. ivette.raices@cigb.edu.cu.
authors.forename: Ivette
authors.initials: I
authors.lastname: Raíces-Cruz
authors.affiliation: Center for Genetic Engineering and Biotechnology (CIGB), Ave. 31 e/ 158 y 190, Cubanacán, Playa, PO Box 6162, Havana, 10 600, Cuba. carmen.valenzuela@cigb.edu.cu.
authors.forename: Carmen
authors.initials: C
authors.lastname: Valenzuela-Silva
authors.affiliation: Laboratory of Immunopharmacology, Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil. mmtex.ufmg@gmail.com.
authors.forename: Mauro Martins
authors.initials: MM
authors.lastname: Teixeira
authors.affiliation: Center for Genetic Engineering and Biotechnology (CIGB), Ave. 31 e/ 158 y 190, Cubanacán, Playa, PO Box 6162, Havana, 10 600, Cuba. eduardo.penton@cigb.edu.cu.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Pentón-Arias
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D007150:Immunohistochemistry; D016899:Interferon-beta / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009416:Nerve Regeneration / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress / Q000187:drug effects; D010798:Phycocyanin / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology
chemical_list: D000893:Anti-Inflammatory Agents; D018696:Neuroprotective Agents; D010798:Phycocyanin; D016899:Interferon-beta
keywords: C-Phycocyanin; EAE; IFN-beta; Multiple sclerosis; Neuroregeneration; Remyelination