Brain injury triggers the endoplasmic reticulum stress response in various cell types at different time periods.

Abstract

Endoplasmic reticulum (ER) stress is caused by the accumulation of misfolded/unfolded proteins in the ER lumen, which leads to the activation of unfolded protein response (UPR), a set of signal transduction pathways. UPR coordinates protein homeostasis through the regulation of protein quality, synthesis, and degradation. Accumulating evidence suggests that the UPR plays an important role in neuropathological conditions such as neurodegenerative diseases and brain insults. However, the cell types and timing of UPR induction in pathogenesis are not fully understood. In this study, we examined the cellular and temporal patterns of the UPR after brain injury using the stab injury model in ER stress-activated indicator (ERAI) mice, which can monitor the UPR by detecting the activity of an ER stress transducer with green fluorescence. The fluorescent signals increased over time in the ipsilateral cortex from 6 hours to 7 days after brain injury in ERAI mice. The reporter signals were observed in injured neurons in the early stages after brain injury. However, the major cells positive for the fluorescent signals were non-neuronal cells such as vascular cells and astrocytes throughout the period analyzed after brain injury. These results suggest that UPR may play important roles not only in neurons but also in the non-neuronal cells in the course of neurological diseases including brain injury.