Activation, Proliferation and Commitment of Endogenous Stem/Progenitor Cells to the Oligodendrocyte Lineage by TS1 in a Rat Model of DysmyelinationEspinosa-Jeffrey A. · Zhao P. · Awosika W. · Wu N. · Macias F. · Cepeda C. · Levine M. · de Vellis J.
Mental Retardation Research Center, Semel Institute for Neuroscience and Human Behavior and Departments of Neurobiology and Psychiatry, University of California, Los Angeles, Calif., USA
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.
Dr. Araceli Espinosa-Jeffrey
Semel Institute for Neuroscience and Human Behavior
Mental Retardation Research Center, 635 Charles E. Young Dr. South
Suite 260G, Neuroscience Research Bldg., Los Angeles, CA 90095-7332 (USA)
Tel. +1 310 825 1747, Fax +1 310 206 5061, E-Mail firstname.lastname@example.org
Received: October 20, 2005
Accepted: October 25, 2005
Number of Print Pages : 11
Number of Figures : 6, Number of Tables : 0, Number of References : 29
Vol. 28, No. 6, Year 2006 (Cover Date: October 2006)
Journal Editor: Campagnoni, A.T. (Los Angeles, Calif.)
ISSN: 0378–5866 (print), 1421–9859 (Online)
For additional information: http://www.karger.com/DNE