Multiple sclerosis patient-derived CSF induces transcriptional changes in proliferating oligodendrocyte progenitors. (November 2015)

• Record Type: Journal Article
• Authors: Haines, Jeffery D; Vidaurre, Oscar G; Zhang, Fan; Riffo-Campos, Ángela L; Castillo, Josefa; Casanova, Bonaventura; Casaccia, Patrizia; Lopez-Rodas, Gerardo
• Is Part Of: Multiple sclerosis. Volume 21:Number 13(2015)
• Page Start: 1655
• Page End: 1669
• Publication Date: 2015-11
• Subjects: Cerebrospinal fluid -- oligodendrocyte progenitor cells -- gene expression -- differentiation; Central nervous system -- Diseases -- Periodicals; Myelin sheath -- Diseases -- Periodicals; Inflammation -- Periodicals; Multiple sclerosis -- Periodicals; Central Nervous System Diseases -- Periodicals; Demyelinating Diseases -- Periodicals; Inflammation -- Periodicals; Multiple Sclerosis -- Periodicals; Système nerveux central -- Maladies -- Périodiques; Gaine de myéline -- Maladies -- Périodiques; Inflammation (Pathologie) -- Périodiques; Sclérose en plaques -- Périodiques; Electronic journals; 616.834005
• DOI: 10.1177/1352458515573094
• Languages: English
• ISSNs: 1352-4585

Abstract

Background: Cerebrospinal fluid (CSF) is in contact with brain parenchyma and ventricles, and its composition might influence the cellular physiology of oligodendrocyte progenitor cells (OPCs) thereby contributing to multiple sclerosis (MS) disease pathogenesis. Objective: To identify the transcriptional changes that distinguish the transcriptional response induced in proliferating rat OPCs upon exposure to CSF from primary progressive multiple sclerosis (PPMS) or relapsing remitting multiple sclerosis (RRMS) patients and other neurological controls. Methods: We performed gene microarray analysis of OPCs exposed to CSF from neurological controls, or definitive RRMS or PPMS disease course. Results were confirmed by quantitative reverse transcriptase polymerase chain reaction, immunocytochemistry and western blot of cultured cells, and validated in human brain specimens. Results: We identified common and unique oligodendrocyte genes for each treatment group. Exposure to CSF from PPMS uniquely induced branching of cultured progenitors and related transcriptional changes, including upregulation ( P <0.05) of the adhesion molecule GALECTIN-3/ Lgals3, which was also detected at the protein level in brain specimens from PPMS patients. This pattern of gene expression was distinct from the transcriptional programme of oligodendrocyte differentiation during development. Conclusions: Despite evidence of morphological differentiation induced by exposure to CSF of PPMS patients, the overall transcriptional response elicited in cultured OPCs was consistent with the activation of an aberrant transcriptional programme.