Imbalance in Sirt1 Alternative Splicing in Response to Chronic Stress during the Adolescence Period in Female Mice

Shir Shlomi, Roni Toledano, Keren Nitzan, Sigal Dror Shahaf, Emanuela P. Break, Dan Frenkel, Ravid Doron

Research output: Contribution to journalArticlepeer-review


Stressful unpredictable life events have been implicated in numerous diseases. It is now becoming clear that some life periods are more vulnerable than others. As adolescence is a sensitive period in brain development, the long-term effects of stress during this period could be significant. We investigated the long-term effects of exposure to unpredictable chronic mild stress in adolescent mice on alternative splicing of Sirtuin 1. One-month-old mice were exposed to 4 weeks of UCMS and examined for anxiety and cognition at the age of 2, 4 and 6 months. We found a rise in anxious behavior immediately after the exposure to stress. Notably, there was a long-term impairment of performance in cognitive tasks and an imbalance in Sirtuin 1 and TrkB receptor alternative splicing in the stress-exposed mice compared with controls. To conclude, our results show that exposure to unpredictable chronic mild stress during adolescence affects cognition in adulthood. Understanding pathways affiliated with stress may help minimize the long-term emotional effects of an unpredictable, stressful event.

Original languageEnglish
Article number4945
JournalInternational Journal of Molecular Sciences
Issue number9
StatePublished - May 2022

Bibliographical note

Funding Information:
Funding: The work was supported by internal research grant from the Open University of Israel (to R.D.) and part of the research was supported by grants from the ministry of science and technology 3-15715 and from the Koret Global Collaboration on Neurodegenerative Disease Research (D.F.).

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.


  • Sirt1
  • TrkB
  • cognition
  • senescence
  • unpredictable stress


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