Neurotrophin-3 promotes proliferation and cholinergic neuronal differentiation of bone marrow- derived neural stem cells via notch signaling pathway
Abstract
Aims Recently, the potential for neural stem cells (NSCs) to be used in the treatment of Alzheimer's disease (AD) has been reported; however, the therapeutic effects are modest by virtue of the low neural differentiation rate. In our study, we transfected bone marrow-derived NSCs (BM-NSCs) with Neurotrophin-3 (NT-3), a superactive neurotrophic factor that promotes neuronal survival, differentiation, and migration of neuronal cells, to investigate the effects of NT-3 gene overexpression on the proliferation and differentiation into cholinergic neuron of BM-NSCs in vitro and its possible molecular mechanism. Main methods BM-NSCs were generated from BM mesenchymal cells of adult C57BL/6 mice and cultured in vitro. After transfected with NT-3 gene, immunofluorescence and RT-PCR method were used to determine the ability of BM-NSCs on proliferation and differentiation into cholinergic neuron; Acetylcholine Assay Kit was used for acetylcholine (Ach). RT-PCR and WB analysis were used to characterize mRNA and protein level related to the Notch signaling pathway. Key findings We found that NT-3 can promote the proliferation and differentiation of BM-NSCs into cholinergic neurons and elevate the levels of acetylcholine (ACh) in the supernatant. Furthermore, NT-3 gene overexpression increase the expression of Hes1, decreased the expression of Mash1 and Ngn1 during proliferation of BM-NSCs. Whereas, the expression of Hes1 was down-regulated, and Mash1 and Ngn1 expression were up-regulated…
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NTF-3 promotes bone marrow neural stem cell proliferation and differentiation into cholinergic neurons.
“Furthermore, it has been reported that NTF-3 promotes bone marrow neural stem cell proliferation and differentiation into cholinergic neurons [123].”
From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [123]
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Imayoshi, I., Sakamoto, M., Yamaguchi, M., Mori, K., & Kageyama, R. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.4987-09.2010 · Cited by 716 · see citing works
Regulation of glioblastoma stem cells by retinoic acid: role for Notch pathway inhibition
Ying, M., Wang, S., Sang, Y., Sun, P., Lal, B., Goodwin, C. R., Guerrero-Cazares, H., Quinones-Hinojosa, A., Laterra, J., & Xia, S. (2011) · Oncogene · doi:10.1038/onc.2011.58 · Cited by 204 · see citing works
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Role of Cholinergic Signaling in Alzheimer’s Disease
Chen, Z.-R., Huang, J.-B., Yang, S.-L., & Hong, F.-F. (2022) · Molecules · doi:10.3390/molecules27061816 · Cited by 922 · see citing works
Quintero, J., Gutiérrez-Casares, J. R., & Álamo, C. (2022) · Neurology and Therapy · doi:10.1007/s40120-022-00392-2 · Cited by 70 · see citing works
“Furthermore, it has been reported that NTF-3 promotes bone marrow neural stem cell proliferation and differentiation into cholinergic neurons [123].”
Background
- Authors
- Yan, Y.-H., Li, S.-H., Gao, Z., Zou, S.-F., Li, H.-Y., Tao, Z.-Y., Song, J., & Yang, J.-X.
- Affiliations
- Liaoning University of Traditional Chinese Medicine (CN)
- Dalian Municipal Central Hospital (CN)
- ORCID
- Song, Jie
- Venue
- Life Sciences
- Publisher
- Elsevier BV
- Published
- 2016-12
- Volume
- 166
- Pages
- 131-138
- ISSN
- 0024-3205 (ISSN-L)
- OpenAlex
- W2528449563
- Cited by
- 38
- References
- 2
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 3 · 2023: 3 · 2022: 4 · 2021: 1 · 2020: 6 · 2019: 4 · 2018: 6 · 2017: 6
- FWCI
- 2.73
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Life Sciences (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81173580)
- Natural Science Foundation of Liaoning Province (201102144, 2013225086)
- Science Foundation of Shenyang City (F11-264-1-42)
- Liaoning Province Excellent Talents Project (5th group, No. 191)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- neurotrophin-3, cell proliferation, Notch signaling, Hes1, ASCL1, Ngn1, acetylcholine, Alzheimer's disease, gene overexpression, autologous cell therapy
- MeSH terms
- Animals, Bone Marrow Cells, Cells, Cultured, Humans, Mice, Inbred C57BL, Transduction, Genetic, Signal Transduction, Up-Regulation, Gene Expression Regulation, Developmental, Neurotrophin 3, Cell Proliferation, Mice, Receptors, Notch, Neurogenesis, Neural Stem Cells, Cholinergic Neurons
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