Oligodendrocyte and microglia transcriptome analysis in a mouse model of encephalopathy of prematurity induced by systemic inflammation

Premature birth is frequently associated with abnormal brain development, leading to brain damage, the most common being diffuse white matter injury. Perinatal neuroinflammation, which relies primarily on microglial activation, contributes to the myelination failure by affecting oligodendrocytes. To better understand the pathophysiological mechanisms involved in encephalopathy of prematurity, we took advantage of a mouse model in which systemic injections of proinflammatory interleukin-1β (IL1B) disrupt oligodendrocyte differentiation, leading to hypomyelination and cognitive deficits. Newborn mice received intraperitoneal injections of IL1B from postnatal day (P) 1 to P5. At P5 and P10, brains were collected from six control (PBS) and six exposed (IL1B) mice; oligodendrocytes and microglial cells were sequentially isolated using antibodies coupled to magnetic beads targeting O4 and CD11b, respectively. Gene expression analysis performed on Agilent microarray revealed that perinatal inflammation induced major changes in gene expression in both cell types. By improving our understanding of the cellular mechanisms involved in encephalopathy of prematurity, this study could ultimately help design neuroprotective strategies. Male swiss mice received intra-peritoneal injections of PBS or IL1B (10ng/g) from post-natal (P) 1 to P4 and once at P5. At P5 (2h after the last injection) or at P10, mice were sacrificed, brain were collected and O4+ oligodendrocytes were first isolated by Magnetic Activated Cell Sorting (MACS technology, Miltenyi), followed by isolation of CD11B+ microglial cells from the negative fraction collected after O4 sorting. Six control (PBS) and six IL1B-treated replicates were collected at P5 and P10 to perform gene expression analysis on Agilent whole genome 8x60K microarrays.