title: The Anti-Aging Protein Klotho Enhances Remyelination Following Cuprizone-Induced Demyelination.
abstract: The current study examined whether overexpression of Klotho (KL) in transgenic mice can enhance remyelination following cuprizone-induced demyelination and improves the clinical outcome in experimental autoimmune encephalomyelitis (EAE). Demyelination was achieved by feeding transgenic mice overexpressing the transmembrane form of Klotho (KL-OE) and wild-type (WT) littermates cuprizone-containing chow for 6 weeks. The animals were then allowed to remyelinate for 3 weeks. Paraphenylenediamine staining and platelets-derived growth factor receptor α (PDGFRα) and glutathione S-transferase pi (GSTpi) immunohistochemistry were performed on corpus callosum (CC) sections for quantification of myelin and progenitor and mature oligodendrocytes, respectively. The EAE model was induced with the MOG35-55 peptide. The animals were scored daily for clinical symptoms for 30 days. Following 6 weeks of demyelination, both KL-OE mice and WT littermates demonstrated almost complete and comparable demyelination of the CC. However, the level of spontaneous remyelination was increased approximately two-fold in KL-OE mice, although no significant differences in the numbers of PDGFRα and GSTpi-positive cells were observed. Following EAE induction, Klotho overexpression did not affect the clinical scores, likely due to the different roles Klotho plays in the brain and spinal cord. Thus, increasing Klotho expression should be considered as a therapy for enhancing remyelination in the brains of individuals with multiple sclerosis.
authors.affiliation: Departments of Biochemistry, Boston University School of Medicine, 72 E Concord St, Silvio O. Conte Building K304, Boston, MA, USA.
authors.forename: Ella
authors.initials: E
authors.lastname: Zeldich
authors.affiliation: Departments of Biochemistry, Boston University School of Medicine, 72 E Concord St, Silvio O. Conte Building K304, Boston, MA, USA.
authors.forename: Ci-Di
authors.initials: CD
authors.lastname: Chen
authors.affiliation: Renovo Neural Inc. Cleveland, Cleveland, OH, 44106, USA.
authors.forename: Robin
authors.initials: R
authors.lastname: Avila
authors.affiliation: Renovo Neural Inc. Cleveland, Cleveland, OH, 44106, USA.
authors.forename: Satish
authors.initials: S
authors.lastname: Medicetty
authors.affiliation: Departments of Biochemistry, Boston University School of Medicine, 72 E Concord St, Silvio O. Conte Building K304, Boston, MA, USA. cabraham@bu.edu.|Pharmacology and Experimental Therapeutics, Boston, MA, 02118, USA. cabraham@bu.edu.
authors.forename: Carmela R
authors.initials: CR
authors.lastname: Abraham
mesh_terms: D000818:Animals; D003337:Corpus Callosum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003471:Cuprizone / Q000633:toxicity; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000378:metabolism*; D005966:Glucuronidase / Q000235:genetics / Q000378:metabolism*; D051549:Glutathione S-Transferase pi / Q000235:genetics / Q000378:metabolism; D000090265:Klotho Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008996:Monoamine Oxidase Inhibitors / Q000633:toxicity; D009186:Myelin Sheath / Q000235:genetics / Q000378:metabolism*; D009836:Oligodendroglia / Q000378:metabolism / Q000473:pathology; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D008996:Monoamine Oxidase Inhibitors; D003471:Cuprizone; D051549:Glutathione S-Transferase pi; C496557:Gstp1 protein, mouse; D020796:Receptor, Platelet-Derived Growth Factor alpha; D005966:Glucuronidase; D000090265:Klotho Proteins
keywords: Multiple sclerosis; Myelin repair; Oligodendrocyte differentiation; Small molecule compounds