Methyl 3,4-Dihydroxybenzoate Induces Neural Stem Cells to Differentiate Into Cholinergic Neurons in vitro
Neural stem cells (NSCs) have been shown as a potential source for replacing degenerated neurons in neurodegenerative diseases. However, the therapeutic potential of these cells is limited by the lack of effective methodologies for controlling their differentiation. Inducing endogenous pools of NSCs...
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Frontiers Media S.A.
2018-12-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fncel.2018.00478/full |
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| author | Jun-Ping Pan Jun-Ping Pan Yang Hu Yang Hu Jia-Hui Wang Yi-Rong Xin Jun-Xing Jiang Ke-Qi Chen Cheng-You Yang Qin Gao Fei Xiao Fei Xiao Li Yan Huan-Min Luo Huan-Min Luo |
| author_facet | Jun-Ping Pan Jun-Ping Pan Yang Hu Yang Hu Jia-Hui Wang Yi-Rong Xin Jun-Xing Jiang Ke-Qi Chen Cheng-You Yang Qin Gao Fei Xiao Fei Xiao Li Yan Huan-Min Luo Huan-Min Luo |
| author_sort | Jun-Ping Pan |
| collection | DOAJ |
| description | Neural stem cells (NSCs) have been shown as a potential source for replacing degenerated neurons in neurodegenerative diseases. However, the therapeutic potential of these cells is limited by the lack of effective methodologies for controlling their differentiation. Inducing endogenous pools of NSCs by small molecule can be considered as a potential approach of generating the desired cell types in large numbers. Here, we reported the characterization of a small molecule (Methyl 3,4-dihydroxybenzoate; MDHB) that selectively induces hippocampal NSCs to differentiate into cholinergic motor neurons which expressed synapsin 1 (SYN1) and postsynaptic density protein 95 (PSD-95). Studies on the mechanisms revealed that MDHB induced the hippocampal NSCs differentiation into cholinergic motor neurons by inhibiting AKT phosphorylation and activating autophosphorylation of GSK3β at tyrosine 216. Furthermore, we found that MDHB enhanced β-catenin degradation and abolished its entering into the nucleus. Collectively, this report provides the strong evidence that MDHB promotes NSCs differentiation into cholinergic motor neurons by enhancing gene Isl1 expression and inhibiting cell cycle progression. It may provide a basis for pharmacological effects of MDHB directed on NSCs. |
| first_indexed | 2024-12-14T11:43:56Z |
| format | Article |
| id | doaj.art-a33b60fef2d04b1986832cdbaa1b834c |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-12-14T11:43:56Z |
| publishDate | 2018-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-a33b60fef2d04b1986832cdbaa1b834c2022-12-21T23:02:41ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022018-12-011210.3389/fncel.2018.00478409820Methyl 3,4-Dihydroxybenzoate Induces Neural Stem Cells to Differentiate Into Cholinergic Neurons in vitroJun-Ping Pan0Jun-Ping Pan1Yang Hu2Yang Hu3Jia-Hui Wang4Yi-Rong Xin5Jun-Xing Jiang6Ke-Qi Chen7Cheng-You Yang8Qin Gao9Fei Xiao10Fei Xiao11Li Yan12Huan-Min Luo13Huan-Min Luo14Department of Pharmacology, College of Basic Medicine, Jinan University, Guangzhou, ChinaDepartment of Neurosurgery, Guangzhou Women and Children’s Medical Center, Guangzhou, ChinaDepartment of Pharmacology, College of Basic Medicine, Jinan University, Guangzhou, ChinaInstitute of Brain Sciences, Jinan University, Guangzhou, ChinaDepartment of Pharmacology, College of Basic Medicine, Jinan University, Guangzhou, ChinaDepartment of Pharmacology, College of Basic Medicine, Jinan University, Guangzhou, ChinaDepartment of Pharmacology, College of Basic Medicine, Jinan University, Guangzhou, ChinaDepartment of Pharmacology, College of Basic Medicine, Jinan University, Guangzhou, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Jinan University, Guangzhou, ChinaDepartment of Pharmacology, College of Basic Medicine, Jinan University, Guangzhou, ChinaDepartment of Pharmacology, College of Basic Medicine, Jinan University, Guangzhou, ChinaInstitute of Brain Sciences, Jinan University, Guangzhou, ChinaGuangzhou Quality R&D Center of Traditional Chinese Medicine, Guangdong Key Laboratory of Plant Resources, School of Life Sciences, Sun Yat-sen University, Guangzhou, ChinaDepartment of Pharmacology, College of Basic Medicine, Jinan University, Guangzhou, ChinaInstitute of Brain Sciences, Jinan University, Guangzhou, ChinaNeural stem cells (NSCs) have been shown as a potential source for replacing degenerated neurons in neurodegenerative diseases. However, the therapeutic potential of these cells is limited by the lack of effective methodologies for controlling their differentiation. Inducing endogenous pools of NSCs by small molecule can be considered as a potential approach of generating the desired cell types in large numbers. Here, we reported the characterization of a small molecule (Methyl 3,4-dihydroxybenzoate; MDHB) that selectively induces hippocampal NSCs to differentiate into cholinergic motor neurons which expressed synapsin 1 (SYN1) and postsynaptic density protein 95 (PSD-95). Studies on the mechanisms revealed that MDHB induced the hippocampal NSCs differentiation into cholinergic motor neurons by inhibiting AKT phosphorylation and activating autophosphorylation of GSK3β at tyrosine 216. Furthermore, we found that MDHB enhanced β-catenin degradation and abolished its entering into the nucleus. Collectively, this report provides the strong evidence that MDHB promotes NSCs differentiation into cholinergic motor neurons by enhancing gene Isl1 expression and inhibiting cell cycle progression. It may provide a basis for pharmacological effects of MDHB directed on NSCs.https://www.frontiersin.org/article/10.3389/fncel.2018.00478/fullmethyl 34-dihydroxybenzoateneural stem cellsdifferentiatecholinergic neuronsGSK3β |
| spellingShingle | Jun-Ping Pan Jun-Ping Pan Yang Hu Yang Hu Jia-Hui Wang Yi-Rong Xin Jun-Xing Jiang Ke-Qi Chen Cheng-You Yang Qin Gao Fei Xiao Fei Xiao Li Yan Huan-Min Luo Huan-Min Luo Methyl 3,4-Dihydroxybenzoate Induces Neural Stem Cells to Differentiate Into Cholinergic Neurons in vitro Frontiers in Cellular Neuroscience methyl 3 4-dihydroxybenzoate neural stem cells differentiate cholinergic neurons GSK3β |
| title | Methyl 3,4-Dihydroxybenzoate Induces Neural Stem Cells to Differentiate Into Cholinergic Neurons in vitro |
| title_full | Methyl 3,4-Dihydroxybenzoate Induces Neural Stem Cells to Differentiate Into Cholinergic Neurons in vitro |
| title_fullStr | Methyl 3,4-Dihydroxybenzoate Induces Neural Stem Cells to Differentiate Into Cholinergic Neurons in vitro |
| title_full_unstemmed | Methyl 3,4-Dihydroxybenzoate Induces Neural Stem Cells to Differentiate Into Cholinergic Neurons in vitro |
| title_short | Methyl 3,4-Dihydroxybenzoate Induces Neural Stem Cells to Differentiate Into Cholinergic Neurons in vitro |
| title_sort | methyl 3 4 dihydroxybenzoate induces neural stem cells to differentiate into cholinergic neurons in vitro |
| topic | methyl 3 4-dihydroxybenzoate neural stem cells differentiate cholinergic neurons GSK3β |
| url | https://www.frontiersin.org/article/10.3389/fncel.2018.00478/full |
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