Neurovascular Interaction Promotes the Morphological and Functional Maturation of Cortical Neurons
Brain microvascular endothelial cells (BMEC) have been found to guide the migration, promote the survival and regulate the differentiation of neural cells. However, whether BMEC promote development and maturation of immature neurons is still unknown. Therefore, in this study, we used a direct endoth...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-09-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fncel.2017.00290/full |
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| author | Kun-Wei Wu Kun-Wei Wu Jia-Lin Mo Jia-Lin Mo Zeng-Wei Kou Zeng-Wei Kou Qi Liu Qi Liu Ling-Ling Lv Ling-Ling Lv Yu Lei Yu Lei Feng-Yan Sun Feng-Yan Sun Feng-Yan Sun |
| author_facet | Kun-Wei Wu Kun-Wei Wu Jia-Lin Mo Jia-Lin Mo Zeng-Wei Kou Zeng-Wei Kou Qi Liu Qi Liu Ling-Ling Lv Ling-Ling Lv Yu Lei Yu Lei Feng-Yan Sun Feng-Yan Sun Feng-Yan Sun |
| author_sort | Kun-Wei Wu |
| collection | DOAJ |
| description | Brain microvascular endothelial cells (BMEC) have been found to guide the migration, promote the survival and regulate the differentiation of neural cells. However, whether BMEC promote development and maturation of immature neurons is still unknown. Therefore, in this study, we used a direct endothelium-neuron co-culture system combined with patch clamp recordings and confocal imaging analysis, to investigate the effects of endothelial cells on neuronal morphology and function during development. We found that endothelial cells co-culture or BMEC-conditioned medium (B-CM) promoted neurite outgrowth and spine formation, accelerated electrophysiological development and enhanced synapse function. Moreover, B-CM treatment induced vascular endothelial growth factor (VEGF) expression and p38 phosphorylation in the cortical neurons. Through pharmacological analysis, we found that incubation with SU1498, an inhibitor of VEGF receptor, abolished B-CM-induced p-p38 upregulation and suppressed the enhancement of synapse formation and transmission. SB203580, an inhibitor of p38 MAPK also blocked B-CM-mediated synaptic regulation. Together these results clearly reveal that the endothelium-neuron interactions promote morphological and functional maturation of neurons. In addition, neurovascular interaction-mediated promotion of neural network maturation relies on activation of VEGF/Flk-1/p38 MAPK signaling. This study provides novel aspects of endothelium-neuron interactions and novel mechanism of neurovascular crosstalk. |
| first_indexed | 2024-12-16T15:54:25Z |
| format | Article |
| id | doaj.art-252baad68de74ac08e20c27e3362658b |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-12-16T15:54:25Z |
| publishDate | 2017-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-252baad68de74ac08e20c27e3362658b2022-12-21T22:25:37ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022017-09-011110.3389/fncel.2017.00290299419Neurovascular Interaction Promotes the Morphological and Functional Maturation of Cortical NeuronsKun-Wei Wu0Kun-Wei Wu1Jia-Lin Mo2Jia-Lin Mo3Zeng-Wei Kou4Zeng-Wei Kou5Qi Liu6Qi Liu7Ling-Ling Lv8Ling-Ling Lv9Yu Lei10Yu Lei11Feng-Yan Sun12Feng-Yan Sun13Feng-Yan Sun14Institute of Biomedical Sciences and Department of Neurobiology, School of Basic Medical Sciences, Shanghai Medical College, Fudan UniversityShanghai, ChinaShanghai Key Laboratory of Clinical Geriatric Medicine, Research Center on Aging and Medicine, Shanghai Medical College, Fudan UniversityShanghai, ChinaShanghai Key Laboratory of Clinical Geriatric Medicine, Research Center on Aging and Medicine, Shanghai Medical College, Fudan UniversityShanghai, ChinaState Key Laboratory of Medical Neurobiology, Fudan UniversityShanghai, ChinaShanghai Key Laboratory of Clinical Geriatric Medicine, Research Center on Aging and Medicine, Shanghai Medical College, Fudan UniversityShanghai, ChinaState Key Laboratory of Medical Neurobiology, Fudan UniversityShanghai, ChinaShanghai Key Laboratory of Clinical Geriatric Medicine, Research Center on Aging and Medicine, Shanghai Medical College, Fudan UniversityShanghai, ChinaState Key Laboratory of Medical Neurobiology, Fudan UniversityShanghai, ChinaShanghai Key Laboratory of Clinical Geriatric Medicine, Research Center on Aging and Medicine, Shanghai Medical College, Fudan UniversityShanghai, ChinaState Key Laboratory of Medical Neurobiology, Fudan UniversityShanghai, ChinaShanghai Key Laboratory of Clinical Geriatric Medicine, Research Center on Aging and Medicine, Shanghai Medical College, Fudan UniversityShanghai, ChinaState Key Laboratory of Medical Neurobiology, Fudan UniversityShanghai, ChinaInstitute of Biomedical Sciences and Department of Neurobiology, School of Basic Medical Sciences, Shanghai Medical College, Fudan UniversityShanghai, ChinaShanghai Key Laboratory of Clinical Geriatric Medicine, Research Center on Aging and Medicine, Shanghai Medical College, Fudan UniversityShanghai, ChinaState Key Laboratory of Medical Neurobiology, Fudan UniversityShanghai, ChinaBrain microvascular endothelial cells (BMEC) have been found to guide the migration, promote the survival and regulate the differentiation of neural cells. However, whether BMEC promote development and maturation of immature neurons is still unknown. Therefore, in this study, we used a direct endothelium-neuron co-culture system combined with patch clamp recordings and confocal imaging analysis, to investigate the effects of endothelial cells on neuronal morphology and function during development. We found that endothelial cells co-culture or BMEC-conditioned medium (B-CM) promoted neurite outgrowth and spine formation, accelerated electrophysiological development and enhanced synapse function. Moreover, B-CM treatment induced vascular endothelial growth factor (VEGF) expression and p38 phosphorylation in the cortical neurons. Through pharmacological analysis, we found that incubation with SU1498, an inhibitor of VEGF receptor, abolished B-CM-induced p-p38 upregulation and suppressed the enhancement of synapse formation and transmission. SB203580, an inhibitor of p38 MAPK also blocked B-CM-mediated synaptic regulation. Together these results clearly reveal that the endothelium-neuron interactions promote morphological and functional maturation of neurons. In addition, neurovascular interaction-mediated promotion of neural network maturation relies on activation of VEGF/Flk-1/p38 MAPK signaling. This study provides novel aspects of endothelium-neuron interactions and novel mechanism of neurovascular crosstalk.http://journal.frontiersin.org/article/10.3389/fncel.2017.00290/fullneurovascular unitbrain developmentco-culturesynaptic functionVEGFp38 MAPK |
| spellingShingle | Kun-Wei Wu Kun-Wei Wu Jia-Lin Mo Jia-Lin Mo Zeng-Wei Kou Zeng-Wei Kou Qi Liu Qi Liu Ling-Ling Lv Ling-Ling Lv Yu Lei Yu Lei Feng-Yan Sun Feng-Yan Sun Feng-Yan Sun Neurovascular Interaction Promotes the Morphological and Functional Maturation of Cortical Neurons Frontiers in Cellular Neuroscience neurovascular unit brain development co-culture synaptic function VEGF p38 MAPK |
| title | Neurovascular Interaction Promotes the Morphological and Functional Maturation of Cortical Neurons |
| title_full | Neurovascular Interaction Promotes the Morphological and Functional Maturation of Cortical Neurons |
| title_fullStr | Neurovascular Interaction Promotes the Morphological and Functional Maturation of Cortical Neurons |
| title_full_unstemmed | Neurovascular Interaction Promotes the Morphological and Functional Maturation of Cortical Neurons |
| title_short | Neurovascular Interaction Promotes the Morphological and Functional Maturation of Cortical Neurons |
| title_sort | neurovascular interaction promotes the morphological and functional maturation of cortical neurons |
| topic | neurovascular unit brain development co-culture synaptic function VEGF p38 MAPK |
| url | http://journal.frontiersin.org/article/10.3389/fncel.2017.00290/full |
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