Glial chromatin alterations during traumatic brain injury contribute to neurodegeneration

How early injury contributes to detrimental consequences on the brain is under much investigation. Using a Drosophila model, we report a mechanism in glia mediated by the JAK/STAT pathway that plays a dual role in the acute response to the injury and the chronic outcome of brain degeneration.

Upon TBI, glial JAK/STAT pathway acutely triggers multiple protective cellular responses and enhances overall animal lifespan by activating transcriptional targets. On the other hand, this pathway also leads to reduced HP1a in glia, suggesting a loss of heterochromatin. Loss of glial HP1a promotes activation of transposable elements (TEs), as well as heterochromatin-embedded genes.