Suppression of activated microglia promotes survival and function of transplanted oligodendroglial progenitors.
To evaluate the functional consequence of microglial activation in vivo, oligodendroglial progenitors were transplanted into the spinal cord of Long Evans shaker, a myelin mutant rat in which myelin defects are associated with progressive microglial activation. Cells grafted into neonatal rats at the initiation of gliosis successfully myelinated axons. However, cells transplanted during peak microglial activation did not lead to myelination due to death of the grafted cells within 3 days after transplantation. Pretreatment of these animals with minocycline, a tetracycline derivative, resulted in cell survival and myelination by the grafted cells. In culture, minocycline did not affect the survival, proliferation, or differentiation of oligodendroglial progenitors. Hence, minocycline likely modulates the function of reactive glia in vivo to promote the survival and myelination of transplanted oligodendroglial progenitors.
Zhang
Su-Chun
SC
Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin 53706, USA.
Goetz
Brian D
BD
Duncan
Ian D
ID
D000818:Animals; D000831:Animals, Newborn; D016380:Brain Tissue Transplantation; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003711:Demyelinating Diseases / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D005911:Gliosis / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects* / Q000502:physiology; D007150:Immunohistochemistry; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008854:Microscopy, Electron; D008911:Minocycline / Q000494:pharmacology / Q000627:therapeutic use; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D009836:Oligodendroglia / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D020318:Rats, Long-Evans; D011922:Rats, Mutant Strains; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D013234:Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure
D008911:Minocycline