scholarly journals ID: 1084 Proliferative and differentiative effects of the Panax vietnamensis ethanol fraction on murine neural stem cells

2017 ◽  
Vol 4 (S) ◽  
pp. 172
Author(s):  
Huy Quang Do ◽  
Nhung Hai Truong ◽  
Thanh Thai Lam ◽  
Linh Thuy Nguyen ◽  
Dung Minh Le ◽  
...  

Background:Ginseng has been known since ancient time for its unique pharmaceutical effects on human health. Modern studies indicated that extracts of ginseng could improve a broad range of pathological conditions including neurodegenerative diseases such as Alzheimer’s or Parkinson’s disease. Panax vietnamensis, a new ginseng species recently discovered in Vietnam, has received much interest due to its high composition of both known and new saponins whose therapeutic effects have not yet fully evaluated. In this study, the proliferative and differentiative effects of different fractions of the extract of Panax vietnamensis on cultured neural stem cells would be assessed. Materials and methods: Fractions from the Panax vietnamensis were prepared following a successive extraction of the raw material using ethanol, n-butanol, ether ethylic, and water, respectively. Potential toxicity and proliferative effects of each fraction were assessed based on the increase in the sphere diameter in before further analyses. The percentage of cells in active phases, cell cycle- or differentiation-associated genes were analyzed using flow cytometry and real-time RT-PCR. Results:Our results revealed that supplementing media with 200 µg/ml of ethanol Panax vietnamensis fraction significantly increased diameters of neurospheres, also maintained the growth rate of the neurospheres compared with the control within the five-day period. Moreover, the results also demonstrated that the ginseng ethanol fraction and a known neurotrophic protein, NGF, affected the differentiation of the neural stem cells.   Conclusion:200 µg/ml ethanol fraction from the extract of Panax vietnamensis most significantly induced the proliferation of cultured neural stem cells. However, the higher concentration of the fraction seemed not to maintain the growth of neurospheres. Regarding differentiation, the ethanol fraction of Vietnamese ginseng possibly shared similar mechanisms with the neurotrophic growth factor.

2019 ◽  
Vol 28 (12) ◽  
pp. 1686-1699 ◽  
Author(s):  
Chongfeng Chen ◽  
Yujia Yang ◽  
Yue Yao

Hyperbaric oxygen (HBO) therapy may promote neurological recovery from hypoxic-ischemic encephalopathy (HIE). However, the therapeutic effects of HBO and its associated mechanisms remain unknown. The canonical Wnt/β-catenin signaling pathways and bone morphogenetic protein (BMP) play important roles in mammalian nervous system development. The present study examined whether HBO stimulates the differentiation of neural stem cells (NSCs) and its effect on Wnt3/β-catenin and BMP2 signaling pathways. We showed HBO treatment (2 ATA, 60 min) promoted differentiation of NSCs into neurons and oligodendrocytes in vitro. In addition, rat hypoxic-ischemic brain damage (HIBD) tissue extracts also promoted the differentiation of NSCs into neurons and oligodendrocytes, with the advantage of reducing the number of astrocytes. These effects were most pronounced when these two were combined together. In addition, the expression of Wnt3a, BMP2, and β-catenin nuclear proteins were increased after HBO treatment. However, blockade of Wnt/β-catenin or BMP signaling inhibited NSC differentiation and reduced the expression of Wnt3a, BMP2, and β-catenin nuclear proteins. In conclusion, HBO promotes differentiation of NSCs into neurons and oligodendrocytes and reduced the number of astrocytes in vitro possibly through regulation of Wnt3/β-catenin and BMP2 signaling pathways. HBO may serve as a potential therapeutic strategy for treating HIE.


2013 ◽  
Vol 30 (3) ◽  
pp. 1101-1106 ◽  
Author(s):  
WONYOUNG KANG ◽  
HO JUN SEOL ◽  
DONG-HO SEONG ◽  
JANDI KIM ◽  
YONGHYUN KIM ◽  
...  

2019 ◽  
Vol 6 (10) ◽  
pp. 3422-3432
Author(s):  
Huy Quang Do ◽  
Nhung Hai Truong ◽  
Thanh Thai Lam ◽  
Linh Thuy Nguyen ◽  
Dung Minh Le ◽  
...  

2022 ◽  
Author(s):  
Sahar Javadi ◽  
Yue Li ◽  
Jie Shen ◽  
Lucy Zhao ◽  
Yao Fu ◽  
...  

Background: Fragile X syndrome (FXS), the most prevalent inherited intellectual disability and one of the most common monogenic form of autism, is caused by a loss of FMRP translational regulator 1 (FMR1). We have previously shown that FMR1 represses the levels and activities of ubiquitin ligase MDM2 in young adult FMR1-deficient mice and treatment by a MDM2 inhibitor Nutlin-3 rescues both hippocampal neurogenic and cognitive deficits in FMR1-deficient mice when analyzed shortly after the administration. However, it is unknown whether Nutlin-3 treatment can have long-lasting therapeutic effects. Methods: We treated 2-month-old young adult FMR1-deficient mice with Nutlin-3 for 10 days and then assessed the persistent effect of Nutlin-3 on both cognitive functions and adult neurogenesis when mice were 6-month-old mature adults. To investigate the mechanisms underlying persistent effects of Nutlin-3, we analyzed proliferation and differentiation of neural stem cells isolated from these mice and assessed the transcriptome of the hippocampal tissues of treated mice. Results: We found that transient treatment with Nutlin-3 of 2-month-old young adult FMR1-deficient mice prevents the emergence of neurogenic and cognitive deficits in mature adult FXS mice at 6-month of age. We further found that the long-lasting restoration of neurogenesis and cognitive function might not be mediated by changing intrinsic properties of adult neural stem cells. Transcriptomic analysis of the hippocampal tissue demonstrated that transient Nultin-3 treatment leads to significant expression changes in genes related to extracellular matrix, secreted factors, and cell membrane proteins in FMR1-deficient hippocampus.


2005 ◽  
Vol 14 (4) ◽  
pp. 193-202 ◽  
Author(s):  
M. Y. Ryu ◽  
M. A. Lee ◽  
Y. H. Ahn ◽  
K. S. Kim ◽  
S. H. Yoon ◽  
...  

Neural stem cells (NSCs) of the central nervous system (CNS) recently have attracted a great deal of interest not only because of their importance in basic research on neural development, but also in terms of their therapeutic potential in neurological diseases, such as Parkinson's disease (PD). To examine if genetically modified NSCs are a suitable source for the cell and gene therapy of PD, an immortalized mouse NSC line, C17.2, was transduced with tyrosine hydroxylase (TH) gene and with GTP cyclohydrolase 1 (GTPCH1) gene, which are important enzymes in dopamine biosynthesis. The expression of TH in transduced C17.2-THGC cells was confirmed by RT-PCR, Western blot analysis, and immunocytochemistry, and expression of GTPCH1 by RT-PCR. The level of L-DOPA released by C17.2-THGC cells, as determined by HPLC assay, was 3793 pmol/106 cells, which is 760-fold higher than that produced by C17.2-TH cells, indicating that GTPCH1 expression is important for L-DOPA production by transduced C17.2 cells. Following the implantation of C17.2-THGcC NSCs into the striata of parkinsonian rats, a marked improvement in amphetamine-induced turning behavior was observed in parkinsonian rats grafted with C17.2-THGC cells but not in the control rats grafted with C17.2 cells. These results indicate that genetically modified NSCs grafted into the brain of the parkinsonian rats are capable of survival, migration, and neuronal differentiation. Collectively, these results suggest that NSCs have great potential as a source of cells for cell therapy and an effective vehicle for therapeutic gene transfer in Parkinson's disease.


2016 ◽  
Vol 36 (12) ◽  
pp. 2134-2145 ◽  
Author(s):  
Takuma Wakai ◽  
Purnima Narasimhan ◽  
Hiroyuki Sakata ◽  
Eric Wang ◽  
Hideyuki Yoshioka ◽  
...  

Previous studies have shown that intraparenchymal transplantation of neural stem cells ameliorates neurological deficits in animals with intracerebral hemorrhage. However, hemoglobin in the host brain environment causes massive grafted cell death and reduces the effectiveness of this approach. Several studies have shown that preconditioning induced by sublethal hypoxia can markedly improve the tolerance of treated subjects to more severe insults. Therefore, we investigated whether hypoxic preconditioning enhances neural stem cell resilience to the hemorrhagic stroke environment and improves therapeutic effects in mice. To assess whether hypoxic preconditioning enhances neural stem cell survival when exposed to hemoglobin, neural stem cells were exposed to 5% hypoxia for 24 hours before exposure to hemoglobin. To study the effectiveness of hypoxic preconditioning on grafted-neural stem cell recovery, neural stem cells subjected to hypoxic preconditioning were grafted into the parenchyma 3 days after intracerebral hemorrhage. Hypoxic preconditioning significantly enhanced viability of the neural stem cells exposed to hemoglobin and increased grafted-cell survival in the intracerebral hemorrhage brain. Hypoxic preconditioning also increased neural stem cell secretion of vascular endothelial growth factor. Finally, transplanted neural stem cells with hypoxic preconditioning exhibited enhanced tissue-protective capability that accelerated behavioral recovery. Our results suggest that hypoxic preconditioning in neural stem cells improves efficacy of stem cell therapy for intracerebral hemorrhage.


2011 ◽  
Vol 39 (1) ◽  
pp. 569-576 ◽  
Author(s):  
Lu Yao ◽  
Xinlin Chen ◽  
Yingfang Tian ◽  
Haixia Lu ◽  
Pengbo Zhang ◽  
...  

Author(s):  
Tomomi Sato ◽  
Takumi Ito ◽  
Hiroshi Handa

Thalidomide, a sedative drug that was once excluded from the market owing to its teratogenic properties, was later found to be effective in treating multiple myeloma. We had previously demonstrated that cereblon (CRBN) is the target of thalidomide embryopathy and acts as a substrate receptor for the E3 ubiquitin ligase complex, Cullin-Ring ligase 4 (CRL4CRBN) in zebrafish and chicks. CRBN was originally identified as a gene responsible for mild intellectual disability in humans. Fetuses exposed to thalidomide in early pregnancy were at risk of neurodevelopmental disorders such as autism, suggesting that CRBN is involved in prenatal brain development. Recently, we found that CRBN controls the proliferation of neural stem cells in the developing zebrafish brain, leading to changes in brain size. Our findings imply that CRBN is involved in neural stem cell growth in humans. Accumulating evidence shows that CRBN is essential not only for the teratogenic effects but also for the therapeutic effects of thalidomide. This review summarizes recent progress in thalidomide and CRBN research, focusing on the teratogenic and therapeutic effects. Investigation of the molecular mechanisms underlying the therapeutic effects of thalidomide and its derivatives, CRBN E3 ligase modulators (CELMoDs), reveals that these modulators provide CRBN the ability to recognize neosubstrates depending on their structure. Understanding the therapeutic effects leads to the development of a novel technology called CRBN-based proteolysis-targeting chimeras (PROTACs) for target protein knockdown. These studies raise the possibility that CRBN-based small-molecule compounds regulating the proliferation of neural stem cells may be developed for application in regenerative medicine.


2021 ◽  
Vol 4 (1) ◽  
pp. 23-41
Author(s):  
Alexandra-Elena Dobranici ◽  
Sorina Dinescu ◽  
Marieta Costache

Specialised cells of the brain are generated from a population of multipotent stem cells found in the forming embryo and adult brain after birth, called neural stem cells. They reside in specific niches, usually in a quiescent, non-proliferating state that maintains their reservoir. Neural stem cells are kept inactive by various cues such as direct cell-cell contacts with neighbouring cells or by soluble molecules that trigger intracellular responses. They are activated in response to injuries, physical exercise, or hypoxia condition, through stimulation of signaling pathways that are usually correlated with increased proliferation and survival. Moreover, mature neurons play essential role in regulating the balance between active and quiescent state by realising inhibitory or activating neurotransmitters. Understanding molecular mechanisms underlying neuronal differentiation is of great importance in elucidating pathological conditions of the brain and treating neurodegenerative disorders that until now have no efficient therapies.


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