Functional central nervous system myelin repair in an adult mouse model of demyelination caused by proteolipid protein overexpression

• Published in: Journal of neuroscience research 2010-06, Vol.88 (8), p.1682-1694
• Main Authors: Espinosa-Jeffrey, A., Hitoshi, S., Zhao, P., Awosika, O., Agbo, C., Olaniyan, E., Garcia, J., Valera, R., Thomassian, A., Chang-Wei, R., Yamaguchi, M., de Vellis, J., Ikenaka, K.
• Format: Article
• Language: English
• Subjects: Amidines - metabolism; Animals; Cell Movement - drug effects; Cells, Cultured; Central Nervous System - metabolism; Central Nervous System - physiopathology; Corpus Callosum - metabolism; Corpus Callosum - transplantation; Culture Media, Conditioned - pharmacology; Demyelinating Diseases - genetics; Demyelinating Diseases - metabolism; Demyelinating Diseases - pathology; Demyelinating Diseases - surgery; Disease Models, Animal; Dose-Response Relationship, Drug; Exploratory Behavior - physiology; Gangliosides - metabolism; Gene Expression Regulation - drug effects; Green Fluorescent Proteins - genetics; Hindlimb - drug effects; Hindlimb - physiopathology; Intercellular Signaling Peptides and Proteins - pharmacology; Intermediate Filament Proteins - genetics; Mice; Mice, Transgenic; Microscopy, Confocal - methods; Myelin Basic Protein - metabolism; Myelin Proteolipid Protein - genetics; Myelin Proteolipid Protein - metabolism; Nerve Tissue Proteins - genetics; Nestin; neural progenitors; Neurofilament Proteins - metabolism; Neuroglia - chemistry; oligodendrocytes; proteolipid protein overexpression; Recovery of Function - drug effects; Recovery of Function - genetics; Recovery of Function - physiology; recruitment of neural stem cells; remyelination; Time Factors
• ISSN: 0360-4012; 1097-4547; 1097-4547
• DOI: 10.1002/jnr.22334

Two types of interventions to remyelinate the adult demyelinated central nervous system were investigated in heterozygous transgenic mice overexpressing the proteolipid protein gene. 1) A cocktail of trophic factors, “TS1,” was directed toward the activation of the endogenous pool of neural progenitors to increase the number of myelinating oligodendrocytes (OL) in the brain. 2) A combinatorial approach in which OL progenitors were coinjected with TS1 into the corpus callosum of wild‐type and He4e transgenic mice that displayed hindlimb paralysis. The levels of locomotor ability in these mice were evaluated after a single treatment. The data showed that a single administration of either one of the interventions had similar therapeutic effects, alleviating the symptoms of demyelination and leading to the recovery of hindlimb function. Histological and immunofluorescent examination of brain sections showed extensive remyelination that was sufficient to reverse hindlimb paralysis in transgenic mice. When the interventions were administered prior to hindlimb paralysis, He4e mice were able to walk up to 1 year of age without paralysis. © 2010 Wiley‐Liss, Inc.