ePoster

Sex-specific attenuated mTOR signaling after acute and chronic sleep loss

Jordan McCarthy, Alexandra Colman, Ashley Leone, Leya Givvines, Sierra Feeney, Olivia Skwierawski, Mihaela Costin, Marie DeCarlo, Cecilia Petruconis, Elizabeth Wash, Jason Grana, Lakshmi Narayanam, Natalie Burkert, Isabella Succi, Jennifer Tudor
FENS Forum 2024(2024)
Messe Wien Exhibition & Congress Center, Vienna, Austria

Conference

FENS Forum 2024

Messe Wien Exhibition & Congress Center, Vienna, Austria

Resources

Authors & Affiliations

Jordan McCarthy, Alexandra Colman, Ashley Leone, Leya Givvines, Sierra Feeney, Olivia Skwierawski, Mihaela Costin, Marie DeCarlo, Cecilia Petruconis, Elizabeth Wash, Jason Grana, Lakshmi Narayanam, Natalie Burkert, Isabella Succi, Jennifer Tudor

Abstract

Memory formation requires translation, which is dependent mammalian target of rapamycin (mTOR) signaling. While it was shown that five hours of acute sleep deprivation attenuates mTOR-mediated translation in the hippocampus of male mice. Interestingly, we found that mTOR activity was also significantly reduced in the cerebellum of acutely sleep deprived male mice. A chronic sleep restriction of 20 hours of REM sleep loss per day for seven days also significantly reduced mTOR activity in the hippocampus and cerebellum of male mice. In female mice, five hours of acute sleep deprivation only significantly reduced mTOR activity in the hippocampus, and not the cerebellum, and chronic sleep restriction did not impact mTOR activity in either brain region, which differs from findings in males. Further, we determined that fluctuating levels of hormones during the female estrous cycle did not affect mTOR activity in control conditions, or after acute sleep deprivation. In both sexes, we also found that 5 hours of acute sleep deprivation significantly reduced hippocampal translation and impaired spatial memory, as measured in the object place recognition task. Work is ongoing to prevent these deficits by utilizing an adeno-associated virus with a mutant form of eukaryotic initiation factor 4E-binding protein 2 (4EBP2) that contain four aspartic acid point mutations at phosphorylation sites, rendering it constitutively inactive and preventing 4EBP2-mediated inhibition of protein synthesis. Our results show that while sleep loss affects mTOR activity in the hippocampus of male and female mice similarly, other brain regions may be differentially affected based on sex.

Unique ID: fens-24/sex-specific-attenuated-mtor-signaling-48325859