title: A mouse model for testing remyelinating therapies.
abstract: Used in combination with immunomodulatory therapies, remyelinating therapies are a viable therapeutic approach for treating individuals with multiple sclerosis. Studies of postmortem MS brains identified greater remyelination in demyelinated cerebral cortex than in demyelinated brain white matter and implicated reactive astrocytes as an inhibitor of white matter remyelination. An animal model that recapitulates these phenotypes would benefit the development of remyelination therapeutics. We have used a modified cuprizone protocol that causes a consistent and robust demyelination of mouse white matter and cerebral cortex. Spontaneous remyelination occurred significantly faster in the cerebral cortex than in white matter and reactive astrocytes were more abundant in white matter lesions. Remyelination of white matter and cerebral cortex was therapeutically enhanced by daily injections of thyroid hormone triiodothyronine (T3). In summary, we describe an in vivo demyelination/remyelination paradigm that can be powered to determine efficacy of therapies that enhance white matter and cortical remyelination.
authors.affiliation: Renovo Neural, Inc., 10000 Cedar Ave., Cleveland, OH 44106, United States. Electronic address: bbai@renovoneural.com.
authors.forename: C Brian
authors.initials: CB
authors.lastname: Bai
authors.affiliation: Renovo Neural, Inc., 10000 Cedar Ave., Cleveland, OH 44106, United States.
authors.forename: Sunny
authors.initials: S
authors.lastname: Sun
authors.affiliation: Renovo Neural, Inc., 10000 Cedar Ave., Cleveland, OH 44106, United States.
authors.forename: Andrew
authors.initials: A
authors.lastname: Roholt
authors.affiliation: Renovo Neural, Inc., 10000 Cedar Ave., Cleveland, OH 44106, United States.
authors.forename: Emily
authors.initials: E
authors.lastname: Benson
authors.affiliation: Renovo Neural, Inc., 10000 Cedar Ave., Cleveland, OH 44106, United States.
authors.forename: Dale
authors.initials: D
authors.lastname: Edberg
authors.affiliation: Renovo Neural, Inc., 10000 Cedar Ave., Cleveland, OH 44106, United States.
authors.forename: Satish
authors.initials: S
authors.lastname: Medicetty
authors.affiliation: Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, United States.
authors.forename: Ranjan
authors.initials: R
authors.lastname: Dutta
authors.affiliation: Renovo Neural, Inc., 10000 Cedar Ave., Cleveland, OH 44106, United States; Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, United States.
authors.forename: Grahame
authors.initials: G
authors.lastname: Kidd
authors.affiliation: Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, United States.
authors.forename: Wendy B
authors.initials: WB
authors.lastname: Macklin
authors.affiliation: Renovo Neural, Inc., 10000 Cedar Ave., Cleveland, OH 44106, United States; Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, United States.
authors.forename: Bruce
authors.initials: B
authors.lastname: Trapp
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology / Q000648:ultrastructure; D001921:Brain / Q000473:pathology* / Q000648:ultrastructure; D002135:Calcium-Binding Proteins / Q000378:metabolism; D003471:Cuprizone / Q000633:toxicity; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology*; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000139:chemically induced; D007166:Immunosuppressive Agents / Q000009:adverse effects; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000633:toxicity; D018991:Myelin Proteolipid Protein / Q000378:metabolism; D012038:Regeneration / Q000187:drug effects / Q000502:physiology*; D020123:Sirolimus / Q000009:adverse effects; D013997:Time Factors; D014284:Triiodothyronine / Q000627:therapeutic use*; D066127:White Matter / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure
chemical_list: C491049:Aif1 protein, mouse; D002135:Calcium-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D007166:Immunosuppressive Agents; D008840:Microfilament Proteins; D008996:Monoamine Oxidase Inhibitors; D018991:Myelin Proteolipid Protein; D014284:Triiodothyronine; D003471:Cuprizone; D020123:Sirolimus
keywords: Differential remyelination; Internodal length; Mice; Myelin; Therapeutic; Ultrastructure