TY - JOUR
T1 - Progesterone modulates mTOR in the hippocampus of mice after traumatic brain injury
AU - Garling, Richard Justin
AU - Watts, Lora Talley
AU - Sprague, Shane
AU - Digicaylioglu, Murat
N1 - Funding Information:
organized and designed the studies. RJG performed experiments and analyzed the data. MD contributed to reagents and supplies necessary for the study. RJG, LTW and MD wrote and edited the article and figures. All authors approved the final version of this paper. Conflicts of interest: The author declare that no competing financial interests exist. Financial support: None. Research ethics: This study was approved by the Institutional Animal Care and Committee of the UTHSCSA (Committee Approval Number 13034X). Data sharing statement: Datasets analyzed during the current study are available from the corresponding author on reasonable request. Plagiarism check: Checked twice by iThenticate. Peer review: Externally peer reviewed. Open access statement: This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-Shar-eAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under identical terms. Open peer reviewer: Seema K. Tiwari-Woodruff, UCR School of Medicine, USA.
Publisher Copyright:
© 2018 Medknow Publications. All rights reserved.
PY - 2018/3
Y1 - 2018/3
N2 - 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.
AB - 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.
KW - Closed skull head injury
KW - Nerve regeneration
KW - Neural regeneration
KW - Neuroprotection
KW - Neurotrauma
KW - Pneumatic injury model
KW - Progesterone
KW - Traumatic brain injury
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U2 - 10.4103/1673-5374.228725
DO - 10.4103/1673-5374.228725
M3 - Article
AN - SCOPUS:85052001104
VL - 13
SP - 434
EP - 439
JO - Neural Regeneration Research
JF - Neural Regeneration Research
SN - 1673-5374
IS - 3
ER -