Brain-derived Neurotrophic Factor Promotes Growth of Neurons and Neural Stem Cells Possibly by Triggering the Phosphoinositide 3-Kinase/ AKT/Glycogen Synthase Kinase-3β/β-catenin Pathway
| Autor: | Shi-Kang Deng, Wang Xianbin, Wei Ma, Li-Yan Li, Wang Tongtong, Dai Yunfei, Zhang Liang, Jin-Wei Yang, Guo Jianhui, Xing-Tong Li |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Neurite Neurogenesis Tropomyosin receptor kinase B Phosphatidylinositol 3-Kinases 03 medical and health sciences 0302 clinical medicine Neural Stem Cells Neurotrophic factors Animals Protein kinase B Cells Cultured beta Catenin PI3K/AKT/mTOR pathway Pharmacology Brain-derived neurotrophic factor Glycogen Synthase Kinase 3 beta Phosphoinositide 3-kinase biology Brain-Derived Neurotrophic Factor General Neuroscience Neural stem cell Rats Cell biology 030104 developmental biology nervous system Cancer research biology.protein Proto-Oncogene Proteins c-akt Cell Division 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | CNS & Neurological Disorders - Drug Targets. 16 |
| ISSN: | 1871-5273 |
| DOI: | 10.2174/1871527316666170518170422 |
| Popis: | Background: Brain-derived neurotrophic factor (BDNF) plays a crucial role in promoting survival and differentiation of neurons and neural stem cells (NSCs), but the downstream regulating mechanisms remain poorly understood. Objective: We investigated whether BDNF exerts its effect by triggering the phosphoinositide 3-kinase (PI3K), protein kinase B, PKB (AKT), glycogen synthase kinase-3β (GSK-3β) and β-catenin signaling pathway in cultured neurons and NSCs derived from the rat embryonic spinal cord. Method: Immunocytochemistry was used to detect neuronal and NSC characteristics. RT-PCR was used to detect PI3K/AKT/GSK3β/β-catenin pathway expression. Results: Neurons and NSCs were successfully separated and cultured from Sprague-Dawley (SD) rat embryonic spinal cord and were respectively labeled using immunocytochemistry. Neuron-specific nuclear protein (NeuN), neuronal class III β-tubulin (Tuj1), and neurofilament expression was detected in neurons; nestin, glial fibrillary acidic protein (GFAP), microtubule-associated protein 2 (Map2) and chondroitin sulfate glycosaminoglycan CSPG (NG2) expression was detected in NSCs. BDNF promoted significant neuronal growth (number, soma size, and average neurite length), as well as NSC proliferation and differentiation, but BDNF antibody decreased neuronal growth and NSC proliferation and differentiation. RT-PCR was used to detect changes in BDNF signal pathway components, showing that BDNF upregulated tropomyosin receptor kinase B (TrkB), phosphoinositide 3-kinase (PI3K), AKT and β-catenin, but downregulated GSK-3β in neurons and NSCs. BDNF antibody downregulated BDNF, tropomyosin receptor kinase B, PI3K, AKT, β-catenin and cellular-myelocytomatosis viral oncogene (c-myc), but upregulated GSK-3β, in neurons and NSCs. Conclusion: Our findings suggested that BDNF contributed to neuronal growth and proliferation and differentiation of NSCs in vitro by stimulating PI3K/AKT/GSK3β/β-catenin pathways. |
| Databáze: | OpenAIRE |
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