title: Fibroblast growth factor 2 mediated disruption of myelin-forming oligodendrocytes in vivo is associated with increased tau immunoreactivity.
abstract: We have previously shown that fibroblast growth factor 2 (FGF2) disrupts myelin formation by oligodendrocytes in vivo. Here, we have investigated the possibility that this is associated with changes in the expression of tau, a major microtubule-associated protein (MAP) involved in the production of myelin membranes by oligodendrocytes. FGF2, or saline vehicle in controls, was delivered into the brain ventricles of deeply anaesthetised young rats, and their actions were examined on the anterior medullary velum (AMV), a thin sheet of tissue that roofs part of the ventricular system underlying the cerebellum. The results show that the FGF2-induced loss of myelin is associated with increased immunostaining for tau within oligodendrocyte somata. Immunohistochemical and Western blot analyses demonstrate a 50% decrease in myelin-forming oligodendrocytes, axonal myelin sheaths, and levels of myelin-related proteins, with a correlative 100% increase in the level of tau. The results identify a potential mechanism by which FGF2-mediated accumulation of tau disrupts the transport of myelin-related gene products, resulting in disruption and eventual loss of oligodendrocytes and myelin, which are features of ischemia and a variety of demyelinating and neurodegenerative diseases.
authors.affiliation: Neurorestoration Group, Wolfson Centre for Age Related Diseases, GKT Guy's Campus, King's College, London SE11UL, UK. arthur.butt@kcl.ac.uk
authors.forename: Arthur M
authors.initials: AM
authors.lastname: Butt
authors.forename: Jennifer
authors.initials: J
authors.lastname: Dinsdale
mesh_terms: D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western / Q000379:methods; D003711:Demyelinating Diseases / Q000139:chemically induced* / Q000378:metabolism; D004334:Drug Administration Schedule; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D007150:Immunohistochemistry / Q000379:methods; D008526:Medulla Oblongata / Q000166:cytology*; D004676:Myelin Basic Protein / Q000378:metabolism; D016900:Neurofilament Proteins / Q000378:metabolism; D009836:Oligodendroglia / Q000187:drug effects* / Q000378:metabolism; D009842:Oligopeptides / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D004676:Myelin Basic Protein; D016900:Neurofilament Proteins; D009842:Oligopeptides; C111711:RNAIII inhibiting peptide; D016875:tau Proteins; D016222:Fibroblast Growth Factor 2; C051774:neurofilament protein H; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases