Progesterone modulates mTOR in the hippocampus of mice after traumatic brain injury

Richard Justin Garling, Lora Talley Watts, Shane Sprague, Murat Digicaylioglu

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

The mechanistic target of rapamycin (mTOR) is an intracellular protein kinase that functions as an energy and nutrient sensor in the cellular microenvironment of neurons. Modulation of mTOR is vital when nutrient and energy sources become limited. Hypoxia, traumatic brain injury, cellular energy states, and growth factors all regulate the phosphorylation and total levels of mTOR in cells. Alterations in the microenvironment induce transduction of signals to downstream proteins by mTOR allowing for cells to make the necessary adjustments to counteract stressors and survive. Progesterone, a hydrophobic steroid hormone, has been shown in studies of non-neural tissue to be a suppressor of mTOR and modulator of mTOR phosphorylation. Our study tested the effects of progesterone on mTOR expression following traumatic brain injury. C57BL/6 mice were treated with progesterone (8 mg/kg) at 1 (intraperitoneal), 6 (subcutaneous), 24 (subcutaneous), and 48 (subcutaneous) hours post closed skull traumatic brain injury. The hippocampus was then harvested 72 hours post injury and prepared for western blot analysis. We found that progesterone significantly decreased total mTOR levels in all groups compared to sham treated with vehicle. This was further confirmed by immunostaining showing decreased cytoplasmic mTOR levels compared to sham. Our study shows progesterone is a significant modulator of mTOR levels in the hippocampus of mice following traumatic brain injury.

Original languageEnglish (US)
Pages (from-to)434-439
Number of pages6
JournalNeural Regeneration Research
Volume13
Issue number3
DOIs
StatePublished - Mar 2018

Keywords

  • Closed skull head injury
  • Nerve regeneration
  • Neural regeneration
  • Neuroprotection
  • Neurotrauma
  • Pneumatic injury model
  • Progesterone
  • Traumatic brain injury

ASJC Scopus subject areas

  • Developmental Neuroscience

Fingerprint Dive into the research topics of 'Progesterone modulates mTOR in the hippocampus of mice after traumatic brain injury'. Together they form a unique fingerprint.

  • Cite this