Spatial and Cellular Characterization of mTORC 1 Activation after Spinal Cord Injury Reveals Biphasic Increase Mainly Attributed to Microglia/Macrophages

Mechanistic target of rapamycin complex 1 ( mTORC 1) is an intracellular kinase complex that regulates energy homeostasis and transcription. Modulation of mTORC 1 has proven beneficial in experimental spinal cord injury, making this molecular target a candidate for therapeutic intervention in spinal cord injury. However, both inactivation and activation of mTORC 1 have been reported beneficial for recovery. To obtain a more complete picture of mTORC 1 activity, we aimed to characterize the spatiotemporal activation pattern of mTORC 1 and identify activation in particular cell types after contusion spinal cord injury in rats. To be able to provide a spatial characterization of mTORC 1 activation, we monitored activation of downstream target S 6. We found robust mTORC 1 activation both at the site of injury and in spinal segments rostral and caudal to the injury. There was constitutive mTORC 1 activation in neurons that was biphasically reduced caudally after injury. We found biphasic mTORC 1 activation in glial cells, primarily activated microglia/macrophages. Furthermore, we found mTORC 1 activation in proliferating cells, suggesting this may be a function affected by mTORC 1 modulation. Our results reveal potential windows of opportunity for therapeutic interference with mTORC 1 signaling and immune cells as targets for inhibition of mTORC 1 in spinal cord injury.