Cellular NeuroscienceResearch PaperLipopolysaccharide-activated microglia induce death of oligodendrocyte progenitor cells and impede their development
Section snippets
Chemicals
LPS (055:B5) and NG-nitro-l-arginine methyl ester (l-NAME) were purchased from Sigma (St. Louis, MO, USA). Dulbecco's Modified Eagle Medium (DMEM)/Ham's F12 and F15 medium, insulin-transferrin-selenium, bovine serum albumin (BSA), penicillin/streptomycin, 2.5% trypsin, and carboxy-H2DCFDA were purchased from Invitrogen (Carlsbad, CA, USA). 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetrazolium hydroxide (XTT) kit and lactate dehydrogenase (LDH) kit were purchased from
LPS-activated microglia-induced acute OPC death was associated with NO
To investigate the interaction between OPCs and microglia after LPS exposure, we first used a microglia-OPC co-culture system that physically separates microglia and OPCs but allows free exchange of molecules between the two culture compartments. As shown in Fig. 1 A and 1 B, no cell death was detected in the control culture over the 48 h period. However, a large amount of OPCs directly underneath the cell culture insert (Fig. 1A: LPS center, also shown in lower magnification in Fig. 1B) died
Discussion
Here we provide evidence that LPS-activated microglia are harmful to OPC. This finding is consistent with many studies showing that activated microglia were deleterious to developing OLs (Pang et al., 2000, Sherwin and Fern, 2005, Domercq et al., 2007, Li et al., 2005). The novel finding of the current study, however, is that we demonstrated that OPC died in two distinct time frames.
Activated microglia rapidly respond as the first line of defense to protect against brain damage. During
Conclusion
This study provides new insight into the mechanisms of OL damage by showing a dynamic OPC death mediated by LPS-activated microglia. Further, the deficiency in trophic support by LPS-activated microglia may contribute to the decrease in OL development.
Acknowledgments
This work was supported partially by HD 35496 from National Institute of Child Health and Human Development; NS 54278 from National Institute of Neurological Disorders and Stroke; and by funds from Newborn Medicine and the Department of Pediatrics, University of Mississippi Medical Center.
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