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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.

brain pathology

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