Glial AP1 is activated with aging and accelerated by traumatic brain injury

The authors show that glial AP1 is initially protective after traumatic brain injury (TBI) but remains active chronically, driving tau pathology and degeneration. Glial AP1 similarly activates with normal aging, suggesting this may be accelerated by TBI. The emergence of degenerative disease after traumatic brain injury (TBI) is often described as an acceleration of normal age-related processes. Whether similar molecular processes occur after injury and in age is unclear. Here, we identify a functionally dynamic and lasting transcriptional response in glia, mediated by the conserved transcription factor AP1. In the early post-TBI period, glial AP1 is essential for recovery, ensuring brain integrity and animal survival. In sharp contrast, chronic AP1 activation promotes human tau pathology, tissue loss and mortality. We show a similar process activates in healthy fly brains with age. In humans, AP1 activity is detected after moderate TBI and correlates with microglial activation and tau pathology. Our data provide key molecular insight into glia, highlighting that the same molecular process drives dynamic and contradictory glia behavior in TBI and possibly age, first acting to protect but chronically promoting disease.

Automated summary

The authors demonstrate that glial AP1 is initially protective after TBI but can lead to tau pathology and degeneration over time. This process may also occur with normal aging, suggesting that TBI could accelerate age-related degenerative processes.