The role of microglia in demyelination: insights into the impact of oligodendrocyte-secreted Serpina3n

Microglia, the primary immune cells of the central nervous system, play critical roles in demyelination process. This study investigates the transcriptional changes in microglia associated with demyelination and examines the role of oligodendrocyte-secreted Serpina3n in modulating microglial responses during this pathological process. Bulk RNA sequencing was conducted on microglia isolated from mice subjected to a 4-week cuprizone diet, a model of demyelination. The experimental groups included: (1) normal control mice (Norm_Ctrl), (2) cuprizone-treated wild-type mice (CPZ_Ctrl), and (3) cuprizone-treated Olig2-Cre Serpina3n flox/flox mice (CPZ_cKO). Microglia were purified from mouse brains using magnetic-activated cell sorting (MACS). The results of this study aim to deepen our understanding of olidodendroglial Serpina3n's role in shaping microglial behavior during demyelination and could inform potential therapeutic strategies for demyelinating diseases. Overall design: Experimental groups: Norm_Ctrl: Microglia isolated from wild-type mice fed with normal diet; CPZ_Ctrl: Microglia isolated from wild-type mice after 4 weeks of cuprizone diet; CPZ_cKO: Microglia isolated from Olig2-Cre Serpina3n flox/flox mice after 4 weeks of cuprizone diet. Microglia were isolated from mouse brains in each group using magnetic-activated cell sorting (MACS). Bulk RNA sequencing was performed on the purified microglia to profile transcriptional changes associated with demyelination and the loss of Serpina3n. Each group has 3 or 4 repeats.