THERAPEUTIC EFFECT OF HYDROGEN SULFIDE ON COGNITIVE DISORDERS IN POLYCYSTIC OVARY SYNDROME: THE ROLE OF THE HIPPOCAMPUS
THERAPEUTIC EFFECT OF HYDROGEN SULFIDE ON COGNITIVE DISORDERS IN POLYCYSTIC OVARY SYNDROME: THE ROLE OF THE HIPPOCAMPUS
Masoud Shahraki,1,*Behjat Seifi,2Farzaneh Kianian,3Sara Mehrsoroush,4Mahdi Hajiaqaei,5
1. MSc of medical physiology at Tehran university of medical sciences 2. Professor of physiology at Tehran university of medical sciences 3. Assistant Professor of physiology at Tehran university of medical sciences 4. PhD of Medical Physiology at Tehran University of Medical Sciences 5. PhD of Medical Physiology at Tehran University of Medical Sciences
Introduction: Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects many women of fertility age. PCOS comes with symptoms such as hirsutism, obesity, insulin resistance, and infertility. In addition to physical symptoms, many women with PCOS experience psychological symptoms such as depression, anxiety, and cognitive disorders. "Cognition" refers to aspects of brain function, including language, attention, memory, learning, decision-making, and problem-solving. In women with PCOS, oxidative stress is often elevated. Oxidative stress occurs when there is an imbalance between free radicals and antioxidants in the body. Free radicals can cause damage to cells, DNA, and lipids. Hydrogen sulfide (H2S) has been identified as a physiological gasotransmitter in the mammalian body. H2S has also been identified as an antioxidant, which slows down the progression of ageing and cognitive disorders.
Methods: In this study, 30 female Wistar rats were divided into three groups, with 10 animals per group. The first group (sham) received carboxymethylcellulose (CMC), which is the letrozole solvent. The second group (PCOS) and the third group (PCOS+NaHS) received letrozole at a dosage of 1mg/kg for 27 consecutive days to induce PCOS. On the 21st day, stereotaxic surgery was performed to cannulate the right lateral ventricle. In the PCOS+NaHS group, after PCOS induction, Intracerebroventricular (ICV) administration of Sodium Hydrosulfide (NaHS), which is a Hydrogen Sulfide Donor, was performed for seven consecutive days. Following this, behavioral tests were conducted, including the Barnes maze for spatial memory, the novel object recognition (NOR) test for diagnostic memory, and the shuttle box test for passive avoidance memory. At the end of the study, oxidative stress biomarkers in the hippocampus tissue, such as malondialdehyde (MDA) using spectrophotometry and superoxide dismutase (SOD) activity using ELISA were analyzed.
Results: On the probe day of the NOR test, rats with PCOS spent less time interacting with novel objects than the control group (p < 0.001). During the probe phase of the Barnes maze, rats with PCOS showed more errors (p < 0.001) and longer escape latency times (p < 0.001) than the control group. In the shuttle box test, rats with PCOS exhibited shorter step-down latency compared to the control group (p < 0.001). However, in the PCOS+NaHS group, ICV administration of NaHS improved these parameters. Treated rats spent more time learning the novel object than the PCOS group during the NOR test probe day (p < 0.001). Additionally, during the probe phase of the Barnes maze, treated rats showed fewer errors (p < 0.01) and shorter escape latency times (p < 0.001) than the PCOS group. In the shuttle box test, treated rats had longer step-down latency times than the PCOS group (p < 0.05). Furthermore, PCOS rats exhibited higher MDA levels (p < 0.001) and lower SOD activity (p < 0.001) in the hippocampus compared to the control group. Treated rats with NaHS showed decreased MDA levels (p < 0.05) and increased SOD activity (p < 0.001) in the hippocampus compared to the PCOS group.
Conclusion: The study indicates that PCOS can lead to cognitive disorders. Oxidative stress is a significant factor in the development of cognitive disorders caused by PCOS. This might be due to the neuroprotective function of estrogen, which plays a role in protecting the brain. Additionally, H2S has been found to have a positive effect on the cognitive function of rats with PCOS. This effect could be attributed to the antioxidant and neuromodulatory properties of H2S in the hippocampus, which is crucial for memory and cognition. Oxidative stress results in elevated MDA levels and reduced SOD activity in the hippocampus, potentially causing damage to neurons and impairing memory and cognition.