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Showing 3 results for Neural Stem Cell
K Negintaji , M Foroozanfar , M Jafarinia , A Ghanbari ,
Volume 28, Issue 5 (9-2023)
Abstract
Background & aim: Pregnenolone acts as a precursor to other steroid hormones and exerts its effect as an anti-inflammatory molecule to maintain immune homeostasis in various inflammatory conditions. In these diseases, a decrease in the level ofP has been observed, which emphasizes its role in neuroprotection and nerve regeneration and its anti-inflammatory role. Accordingly, the purpose of the present study was to determine the ability of Pregnenolone in the proliferation of mouse neural stem cells and reduce inflammatory and oxidant markers. of inducing inflammation with lipopolysaccharide in laboratory conditions.
Methods: In the present experimental study conducted at Yasuj University of Medical Sciences, neural stem cells (NSCs) were isolated from the embryonic cortex of E14 mice with standard protocol and incubated for 5 days. Subsequently, neurosphere formation and propagation for second passage the survival of the cells was done after pregnenolone combined treatment with lipopolysaccharide (LPS) inflammatory model. The number of neurospheres and cells derived from neurospheres were counted after 5 days of incubation in the inflammatory model. The supernatant of the cells was removed and the levels of oxidant and antioxidant markers MDA, NO FRAP, and inflammatory markers IL6 and TNFα were measured by ELISA method. Data were analyzed by one-way variance statistical method and Tukey's post hoc test.
Results: The results indicated that pregnenolone with its effect on inflammatory factors could increase the proliferation of neural stem cells in conditions of inflammation and the greatest effect was observed in the group treated with 10 μM dose of pregnenolone with an increase of 68% compared to the LPS group. On the other hand, it caused a decrease in the inflammatory factors TNF-α (12%) and IL-6 (30%) and oxidative stress factors including NO (38%) and MDA (20%) compared to the LPS group, as well as a significant increase FRAP was an antioxidant marker (P<0.0001) in the model of inflammation caused by LPS in the culture medium of mouse neural stem cells.
Conclusion: The results of the present study indicated that Pregnenolone, by affecting inflammatory factors, increased the proliferation of neural stem cells in the conditions of inflammation, and it was as well able to reduce the amount of inflammatory and oxidant markers in the inflammatory model of the culture medium.
Dr Amir Ghanbari, Dr Mehrzad Jafari Barmak, Dr Sanaz Bagheri, Dr Saeid Javedansirat,
Volume 30, Issue 1 (1-2025)
Abstract
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.
Dr Amir Ghanbari, Dr Mehrzad Jafari Barmak, Dr Hassan Bardania,
Volume 30, Issue 3 (4-2025)
Abstract
Background:
Neurogenesis must be continuous and dynamic throughout each individual's life so that the efficiency of different brain parts does not become weak and ineffective. On the other hand, protecting old neurons can also be a solution, so synthetic substances simultaneously having both protective and neurogenic functions can be a good option for targeted drug delivery in brain diseases and aging. In particular, agmatine has a beneficial role in protecting and neurogenic roles due to its role as a polyamine precursor and its ability to cross the blood-brain barrier while inhibiting nitric oxide synthase, and previous studies have also reported a protective and neurogenic role. Therefore, this study aimed to target drug delivery with nanoliposomes and investigate its effects on the proliferation and differentiation of neural stem cells.
Materials and methods
In this experimental-in vitro study, neural stem cells were first isolated from the subventricular zone of the adult mouse brain and proliferated and neurospheres were formed in the presence of epidermal growth factor and fibroblast growth factor. Cell viability was measured in six groups including the control group, a nanoliposome group, an agmatine group with concentrations of (25 and 50) micromolar, and nanoliposome groups treated with agmatine with concentrations of (25 and 50) micromolar by the MTT method. Also, the number of neurospheres, the number of cells resulting from each neurosphere, and the number of neuronal and glial cells following differentiation were counted. The collected data were analyzed using a one-way variance test.
Result:
The cell survival of neural stem cells in the agmatine groups increased in a dose-dependent manner, with a significant increase in the 50 and 100 μM groups compared to the 10 μM agmatine group (**p<0.01). The mean number of neurospheres in the nanoliposome-agmatine 50 μM groups showed a significant increase compared to the liposome and control groups (*p<0.05, **p<0.01). The mean number of neuronal cells in the nanoliposome-agmatine 25 and 50 groups showed a significant increase compared to the liposome and control groups (***p<0.0001).
Conclusion:
The data from this study showed that treatment with agmatine and nano-liposomes containing agmatine can be effective in the proliferation and differentiation of stem cells, and that this increase in proliferation and differentiation in the targeted method with liposomes was effective at a lower concentration of agmatine, which may indicate the targeting of the liposomal system and its value.
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