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The efficacy of fluvoxamine in preventing the aging process of mouse neural stem cells in a di-galactose-induced model in a culture medium
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Amir Ghanbari   1, Mehrzad Jafari barmak , Sanaz Bagheri , Saeid Javedansirat |
| 1- , amirghanbari52@yahoo.com |
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Abstract: (118 Views) |
Background: Cellular senescence is an irreversible process in cells that is affected by various factors such as oxidative stress and inflammation, and the importance of this issue increases in its effect on neural stem cells. Fluvoxamine at appropriate concentrations provides proliferation and differentiation of neural stem cells into glial and neurons and modulates inflammatory factors. Therefore, considering the mechanism of the aging process on neural stem cells, this study investigates the effects of fluvoxamine in culture.
Materials and methods: In this experimental study, neural stem cells were first isolated from the subventricular zone of the adult male mouse brain. Neutrosphere cell colonies were formed in the presence of epidermal growth factor and fibroblast growth factor. The survival of neurospheres in fifteen groups including a control group, treatment group with 20 μM D-galactose concentration, and fluvoxamine treatment groups with different concentrations and combined D-galactose with fluvoxamine groups was measured by the MTT method. Also, the number of neurospheres, the number of cells resulting from each neutrosphere cell, and the number of senescent cells were counted. The collected data were analyzed using GraphPad software and a one-way ANOVA test.
Results: The average data from the survival of neural stem cells in the 25 and 50 nM fluvoxamine groups significantly increased compared to the control group and decreased significantly with increasing doses (p<0.001). Also, the survival of cells in the D-galactose group significantly decreased compared to the control group (p<0.01), which showed a significant increase in the treatment with low-dose fluvoxamine compared to the D-galactose group (p<0.001) and a significant decrease in the high-dose groups. The number of neurospheres in the D-galactose group was significantly decreased compared to the control group (p<0.001). Also, the number of neurospheres in the D-galactose group with 50 nM fluvoxamine compared to the D-galactose group was significantly increased (p<0.01). The number of BrdU-positive cells in the fluvoxamine 100 group showed a statistically significant increase compared to the control group (p<0.001). The number of BrdU-positive cells in the di-galactose group also showed a statistically significant decrease compared to the control group (p<0.01). The combination treatment of di-galactose with fluvoxamine at low doses increased the number of BrdU-positive cells compared to the di-galactose group. The average number of neural stem cells in the di-galactose groups decreased significantly compared to the control group, and the combination of di-galactose with fluvoxamine at doses of 50 showed a statistical increase compared to the di-galactose group (p<0.001). The average number of senescent cells increased significantly with increasing fluvoxamine doses compared to the control group. Also, treatment with di-galactose increased the number of senescent cells compared to the control group, and treatment with di-galactose and fluvoxamine at concentrations of 25 and 50 nM showed a statistically significant decrease in the number of senescent cells compared to the di-galactose group (p<0.0001).
Conclusion: The results of this study indicate that fluvoxamine, prescribed for the treatment of major depression and obsessive-compulsive disorders, while increasing the survival and viability of cells at low doses, exhibits significant toxicity at higher doses in a dose-dependent manner. Furthermore, it elevates aging-related factors and induces aging in neural stem cells under ex vivo conditions. In other words, it reduces the survival of neural stem cells, the number of neurospheres, and the number of cells derived from each neurosphere, while simultaneously increasing the number of aged cells. These findings necessitate further investigations in both in vivo and in vitro environments.
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| Keywords: Fluvoxamine, Aging, D-galactose, neural stem cells |
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Type of Study: Research |
Subject:
Anatomy
Received: 2024/08/25 | Accepted: 2024/12/15 | Published: 2025/02/4
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