Abstract
Demyelination is prominent in experimental autoimmune encephalomyelitis (EAE). The
receptor p75 and its high affinity ligand proNGF are required for oligodendrocyte
death after injury. We hypothesize that bone marrow stromal cells (BMSCs) provide
therapeutic benefit in EAE mice by reducing proNGF/p75 expression. PBS or BMSCs (2×10^6) were administered intravenously on the day of EAE onset. Neurological function
and demyelination areas were measured. Immunohistochemical staining was used to measure
apoptotic oligodendrocytes, expression of proNGF and p75, and the relationship between
proNGF and p75 in neural cells. proNGF was used to treat oligodendrocytes in culture
with or without BMSCs. EAE mice exhibited neurological function deficit and demyelination,
and expression of proNGF and p75 was increased. BMSC treatment improved functional
recovery, reduced demyelination area and apoptotic oligodendrocytes, decreased expression
of proNGF and p75 compared with PBS treatment. proNGF+ cells colocalized with neural cell markers, while p75 colocalized with an oligodendrocytic
marker, and proNGF colocalized with p75. proNGF induced apoptosis of oligodendrocytes
in vitro, and p75 antibody blocked this apoptotic activity. BMSCs reduced p75 expression
and apoptotic activity in oligodendrocytes with proNGF treatment. BMSC treatment benefits
on EAE mice may be fostered by decreasing the cellular expression of proNGF and p75,
thereby reducing oligodendrocyte death.
Keywords
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Article info
Publication history
Published online: February 04, 2009
Accepted:
December 23,
2008
Received in revised form:
December 19,
2008
Received:
July 24,
2008
Footnotes
☆This work was supported by NIH grants P01 NS42345 and P01 NS23393 and the Benson Ford Foundation and the Wollowick Foundation (CB).
Identification
Copyright
© 2008 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
