Macrophage-depletion induced impairment of experimental CNS remyelination is associated with a reduced oligodendrocyte progenitor cell response and altered growth factor expression.
Although macrophages are mediators of CNS demyelination, they are also implicated in remyelination. To examine the role of macrophages in CNS remyelination, adult rats were depleted of monocytes using clodronate liposomes and demyelination induced in the spinal cord white matter using lysolecithin. In situ hybridization for scavenger receptor-B and myelin basic protein (MBP) revealed a transiently impaired macrophage response associated with delayed remyelination in liposome-treated animals. Macrophage reduction corresponded with delayed recruitment of PDGFRalpha+ oligodendrocyte progenitor cells (OPCs), which preceded changes in myelin phagocytosis, indicating a macrophage effect on OPCs independent of myelin debris clearance. Macrophage-depletion induced changes in the mRNA expression of insulin-like growth factor-1 and transforming growth factor beta1, but not platelet-derived growth factor-A and fibroblast growth factor-2. These data suggest that the macrophage response to toxin-induced demyelination influences the growth factor environment, thereby affecting the behavior of OPCs and hence the efficiency of remyelination.
Kotter
Mark R
MR
Cambridge Centre for Brain Repair, and Neuroregeneration Laboratory, Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 0ES, UK.
Zhao
Chao
C
van Rooijen
Nico
N
Franklin
Robin J M
RJ
D000818:Animals; D002490:Central Nervous System / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D003711:Demyelinating Diseases / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000502:physiology; D005260:Female; D006133:Growth Substances / Q000235:genetics* / Q000378:metabolism; D008264:Macrophages / Q000502:physiology*; D004676:Myelin Basic Protein / Q000235:genetics; D009186:Myelin Sheath / Q000378:metabolism / Q000473:pathology; D009416:Nerve Regeneration / Q000502:physiology*; D009836:Oligodendroglia / Q000378:metabolism* / Q000473:pathology; D010587:Phagocytosis / Q000235:genetics; D012313:RNA / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics; D051116:Receptors, Scavenger; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology
D006133:Growth Substances; D004676:Myelin Basic Protein; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D012313:RNA; D020796:Receptor, Platelet-Derived Growth Factor alpha