Activation, proliferation and commitment of endogenous stem/progenitor cells to the oligodendrocyte lineage by TS1 in a rat model of dysmyelination.
Wild-type and myelin-deficient rats received a single intraparenchymal injection of TS1, a specific combination of IGF-1 and transferrin (Tf), into their corpus callosum at postnatal day 4. The fate of endogenous stem cells in the brain was examined by the expression of the stem cell marker nestin, together with Tf, neurofilaments and glial fibrillary acidic protein from 2 to 14 days after injection. Treated mutants lacked nestin expression in the ventricular wall and had an increase in nestin-labeled radial cell processes in the subventricular regions, and extended into the parenchyma. The subventricular zone was populated by healthy new oligodendrocytes (OLs). BrdU incorporation showed that these cells originated by proliferation and were identified as OLs based upon Tf expression. Thus, TS1 is an effective treatment to promote endogenous subventricular zone progenitor proliferation, migration and OL lineage specification. This strategy offers for the first time the possibility of myelin restoration to treat myelin disorders.
Espinosa-Jeffrey
Araceli
A
Mental Retardation Research Center, Semel Institute for Neuroscience and Human Behavior and Department of Neurobiology, University of California, Los Angeles, 90095-7332, USA. aespinosa@mednet.ucla.edu
Zhao
Paul
P
Awosika
Wole
W
Wu
Nanping
N
Macias
Fernando
F
Cepeda
Carlos
C
Levine
Michael
M
de Vellis
Jean
J
D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D019070:Cell Lineage / Q000187:drug effects / Q000502:physiology*; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects* / Q000254:growth & development* / Q000378:metabolism; D003337:Corpus Callosum / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D003711:Demyelinating Diseases / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007381:Intermediate Filament Proteins / Q000378:metabolism; D020547:Lateral Ventricles; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D016900:Neurofilament Proteins / Q000378:metabolism; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011922:Rats, Mutant Strains; D017208:Rats, Wistar; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism*; D013687:Telencephalon / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D014168:Transferrin / Q000494:pharmacology
D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D007381:Intermediate Filament Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; D016900:Neurofilament Proteins; D014168:Transferrin; D007334:Insulin-Like Growth Factor I