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Updated: Sep 8, 2025
Author Spotlight: Investigating the Mechanisms and Inducing Models of Polycystic Ovary Syndrome
Published on: July 5, 2024
Sirtuins, redox, and metabolic pathways in the brain of female PCOS mice
Teresa Vergara1, Giovanni Casoli1, Andrea Bianchi1
1Department of Life, Health and Environmental Sciences, University of L'Aquila, 67100, L'Aquila, Italy.
Purpose:
Recent studies emphasize the role of neuroendocrine dysfunctions and sirtuins in polycystic ovarian syndrome (PCOS). We investigated whether altered SIRT1 and SIRT3 levels contribute to brain changes and oxidative stress, identifying these pathways as potential therapeutic targets for PCOS-related complications.
Methods:
Using a DHEA-induced PCOS mouse model, we examined brain expression of pathways related to SIRT1 and SIRT3 and to oxidative/glycative stress changes. SH-SY5Y cells treated with DHEA were used to confirm direct neuronal effects.
Results:
We found decreased levels of Sirt1 and Sirt3 transcripts but increased protein expression and activity of both sirtuins in brains of DHEA-treated mice. The DHEA group showed elevated oxidative and glycative stress, including an overall increased lipid peroxidation and DNA damage, as well as accumulation of advanced glycation endproducts (AGEs) in isocortices. Differences in Cpt1 isoform expressions suggested disrupted metabolic processing in the PCOS brains. Neuronal degeneration was also observed, alongside unchanged Bdnf and TrkB mRNA levels in DHEA brains. Exposure of differentiated SH-SY5Y neuron-like cells to high concentrations (≥ 100 µM) led to increased oxidative stress, altered sirtuins expression, and ultimately cell toxicity. While low concentrations of DHEA (1 µM) did not elicit such responses.
Conclusions:
These findings reveal a complex interplay between oxidative stress, metabolic dysregulation, and neuronal health in PCOS brain, underscoring the need for further investigations into the underlying mechanisms, including research in genetic components. This research provides foundational insights into how PCOS may influence neurobiological processes and helps clarify some aspects of its pathogenesis.
Insights
Polycystic ovary syndrome (PCOS) is linked to brain changes and oxidative stress, involving sirtuins (SIRT1 and SIRT3). This study reveals complex neurobiological impacts of PCOS, highlighting potential therapeutic targets.
Area of Science:
- Neuroendocrinology
- Molecular Biology
- Cell Biology
Background:
- Polycystic ovary syndrome (PCOS) is associated with neuroendocrine dysfunctions.
- Sirtuins (SIRT1 and SIRT3) are implicated in PCOS pathogenesis.
- PCOS complications may involve central nervous system alterations.
Purpose of the Study:
- To investigate the role of altered SIRT1 and SIRT3 levels in PCOS-related brain changes.
- To examine the contribution of oxidative and glycative stress to PCOS neurobiology.
- To identify potential therapeutic targets for PCOS-related neurological complications.
Main Methods:
- A DHEA-induced PCOS mouse model was used to assess brain expression of SIRT1, SIRT3, and oxidative/glycative stress markers.
- SH-SY5Y cells were treated with DHEA to evaluate direct neuronal effects.
- Analysis included transcript and protein expression, oxidative stress markers, lipid peroxidation, DNA damage, advanced glycation endproducts (AGEs), and Cpt1 isoform expression.
Main Results:
- DHEA-induced PCOS mice exhibited decreased Sirt1 and Sirt3 transcripts but increased protein expression and activity.
- Elevated oxidative and glycative stress, lipid peroxidation, DNA damage, and AGEs accumulation were observed in PCOS brains.
- Neuronal degeneration occurred, with altered Cpt1 isoform expression suggesting metabolic disruption; SH-SY5Y cells showed toxicity at high DHEA concentrations.
Conclusions:
- PCOS involves a complex interplay of oxidative stress, metabolic dysregulation, and neuronal health in the brain.
- Sirtuin pathways are significantly altered in the PCOS brain, contributing to neurobiological changes.
- Further research into genetic components and underlying mechanisms is crucial for understanding PCOS pathogenesis and developing therapeutic strategies.
