title: BLBP-expression in astrocytes during experimental demyelination and in human multiple sclerosis lesions.
abstract: Several lines of evidence indicate that remyelination represents one of the most effective mechanisms to achieve axonal protection. For reasons that are not yet understood, this process is often incomplete or fails in multiple sclerosis (MS). Activated astrocytes appear to be able to boost or inhibit endogenous repair processes. A better understanding of remyelination in MS and possible reasons for its failure is needed. Using the well-established toxic demyelination cuprizone model, we created lesions with either robust or impaired endogenous remyelination capacity. Lesions were analyzed for mRNA expression levels by Affymetrix GeneChip® arrays. One finding was the predominance of immune and stress response factors in the group of genes which were classified as remyelination-supporting factors. We further demonstrate that lesions with impaired remyelination capacity show weak expression of the radial-glia cell marker brain lipid binding protein (BLBP, also called B-FABP or FABP7). The expression of BLBP in activated astrocytes correlates with the presence of oligodendrocyte progenitor cells. BLBP-expressing astrocytes are also detected in experimental autoimmune encephalomyelitis during the remission phase. Furthermore, highest numbers of BLBP-expressing astrocytes were evident in lesions of early MS, whereas significantly less are present at the rim of (chronic)-active lesions from patients with long disease duration. Transfection experiments show that BLBP regulates growth factor expression in U87 astrocytoma cells. In conclusion, we provide evidence that expression of BLBP in activated astrocytes negatively correlates with disease duration and in parallel with remyelination failure.
authors.affiliation: Institute of Neuroanatomy, Faculty of Medicine, RWTH Aachen University, Wendlingweg 2, D-52074 Aachen, Germany. mkipp@ukaachen.de
authors.forename: M
authors.initials: M
authors.lastname: Kipp
authors.forename: S
authors.initials: S
authors.lastname: Gingele
authors.forename: F
authors.initials: F
authors.lastname: Pott
authors.forename: T
authors.initials: T
authors.lastname: Clarner
authors.forename: P
authors.initials: P
authors.lastname: van der Valk
authors.forename: B
authors.initials: B
authors.lastname: Denecke
authors.forename: L
authors.initials: L
authors.lastname: Gan
authors.forename: V
authors.initials: V
authors.lastname: Siffrin
authors.forename: F
authors.initials: F
authors.lastname: Zipp
authors.forename: W
authors.initials: W
authors.lastname: Dreher
authors.forename: W
authors.initials: W
authors.lastname: Baumgartner
authors.forename: S
authors.initials: S
authors.lastname: Pfeifenbring
authors.forename: R
authors.initials: R
authors.lastname: Godbout
authors.forename: S
authors.initials: S
authors.lastname: Amor
authors.forename: C
authors.initials: C
authors.lastname: Beyer
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D015153:Blotting, Western; D002352:Carrier Proteins / Q000096:biosynthesis*; D002452:Cell Count; D045744:Cell Line, Tumor; D003471:Cuprizone; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins / Q000096:biosynthesis*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis / Q000235:genetics; D019084:Fluorescent Antibody Technique, Indirect; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000378:metabolism* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D020411:Oligonucleotide Array Sequence Analysis; D053495:Osteopontin / Q000096:biosynthesis; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis*
chemical_list: D002352:Carrier Proteins; C107608:FABP7 protein, human; C086936:Fabp7 protein, mouse; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; C075278:platelet-derived growth factor A; D016222:Fibroblast Growth Factor 2; D053495:Osteopontin; D003471:Cuprizone