Developmental stage of oligodendrocytes determines their response to activated microglia in vitro.
BACKGROUND
Oligodendrocyte progenitor cells (OPCs) and mature oligodendrocytes are both lost in central nervous system injury and disease. Activated microglia may play a role in OPC and oligodendrocyte loss or replacement, but it is not clear how the responses of OPCs and oligodendrocytes to activated microglia differ.


METHODS
OPCs and microglia were isolated from rat cortex. OPCs were induced to differentiate into oligodendrocytes with thyroid hormone in defined medium. For selected experiments, microglia were added to OPC or oligodendrocyte cultures. Lipopolysaccharide was used to activate microglia and microglial activation was confirmed by TNFalpha ELISA. Cell survival was assessed with immunocytochemistry and cell counts. OPC proliferation and oligodendrocyte apoptosis were also assessed.


RESULTS
OPCs and oligodendrocytes displayed phenotypes representative of immature and mature oligodendrocytes, respectively. Activated microglia reduced OPC survival, but increased survival and reduced apoptosis of mature oligodendrocytes. Activated microglia also underwent cell death themselves.


CONCLUSIONS
Activated microglia may have divergent effects on OPCs and mature oligodendrocytes, reducing OPC survival and increasing mature oligodendrocyte survival. This may be of importance because activated microglia are present in several disease states where both OPCs and mature oligodendrocytes are also reacting to injury. Activated microglia may simultaneously have deleterious and helpful effects on different cells after central nervous system injury.
Brain and Spinal Injury Center, Department of Neurological Surgery, University of California San Francisco, 1001 Potrero Ave, Building 1, Room 101, San Francisco, CA 94143, USA. Brandon.Miller@osumc.edu
Brandon A
BA
Miller
Jeannine M
JM
Crum
C Amy
CA
Tovar
Adam R
AR
Ferguson
Jacqueline C
JC
Bresnahan
Michael S
MS
Beattie
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D020170:Caspase 1 / Q000378:metabolism; D002450:Cell Communication; D016923:Cell Death / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D017628:Microglia / Q000502:physiology*; D009836:Oligodendroglia / Q000502:physiology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology*; D013963:Thyroid Hormones / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D008070:Lipopolysaccharides; D010982:Platelet-Derived Growth Factor; D013963:Thyroid Hormones; D014409:Tumor Necrosis Factor-alpha; D005346:Fibroblast Growth Factors; D020170:Caspase 1