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Serotonin Type 3 Receptor Is Potentially Involved in Cellular Stress Induced by Hydrogen Peroxide
Ana Salomé Correia1,2,3, Isabel Silva4, José Carlos Oliveira4,5
1OncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Doutor Plácido da Costa, 4200-450 Porto, Portugal.
Abstract:
Depression is a disease with several molecular mechanisms involved, such as problems in the serotonergic pathway. This disease is very complex and prevalent, and thus important to deeply study and aim to overcome high rates of relapse and therapeutic failure. In this study, two cellular lines were used (HT-22 and SH-SY5Y cells) to gain insight about the role of the serotonin type 3 (5-HT3) receptor in cellular stress induced by hydrogen peroxide and/or corticosterone. In research, these compounds are known to mimic the high levels of oxidative stress and dysfunction of the hypothalamus-hypophysis-adrenal axis by the action of glucocorticoids, usually present in depressed individuals. The receptor 5-HT3 is also known to be involved in depression, previously demonstrated in studies that highlight the role of these receptors as promising targets for antidepressant therapy. Indeed, the drugs used in this work (mirtazapine, scopolamine, and lamotrigine) interact with this serotonergic receptor. Thus, by using cell morphology, cell viability (neutral red and MTT), and HPLC assays, this work aimed to understand the role of these drugs in the stress induced by H2O2/corticosterone to HT-22 and SH-SY5Y cell lines. We concluded that the antagonism of the 5-HT3 receptor by these drugs may be important in the attenuation of H2O2-induced oxidative stress to the cells, but not in the corticosterone-induced stress.
Insights
Antagonism of the serotonin type 3 (5-HT3) receptor by mirtazapine, scopolamine, and lamotrigine may reduce hydrogen peroxide-induced oxidative stress in cells. This suggests a potential therapeutic role for 5-HT3 receptor antagonists in managing cellular stress related to depression.
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- Depression involves complex molecular mechanisms, including the serotonergic pathway and hypothalamic-pituitary-adrenal axis dysfunction.
- Oxidative stress and elevated glucocorticoids, mimicking conditions in depressed individuals, are key factors.
- The serotonin type 3 (5-HT3) receptor is implicated in depression and represents a potential therapeutic target.
Purpose of the Study:
- To investigate the role of the 5-HT3 receptor in cellular stress induced by hydrogen peroxide (H₂O₂) and corticosterone.
- To evaluate the effects of mirtazapine, scopolamine, and lamotrigine on these cellular stress models.
Main Methods:
- Utilized HT-22 and SH-SY5Y cell lines.
- Assessed cellular stress using cell morphology, neutral red, MTT assays, and High-Performance Liquid Chromatography (HPLC).
- Investigated the impact of H₂O₂ and corticosterone exposure, with and without specific drug treatments.
Main Results:
- Drug-induced antagonism of the 5-HT3 receptor showed a potential role in attenuating H₂O₂-induced oxidative stress.
- The protective effect was observed specifically against H₂O₂-induced stress, not corticosterone-induced stress.
Conclusions:
- 5-HT3 receptor antagonism may be a significant factor in mitigating H₂O₂-induced cellular oxidative stress.
- These findings highlight the specific role of 5-HT3 receptor antagonism in cellular stress response, particularly against oxidative insults.
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