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Neuropilin-1 promotes mitochondrial structural repair and functional recovery in rats with cerebral ischemia
OBJECTIVES: Available literature documents that ischemic stroke can disrupt the morphology and function of mitochondria and that the latter in other disease models can be preserved by neuropilin-1 (NRP-1) via oxidative stress suppression. However, whether NRP-1 can repair mitochondrial structure and...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10155168/ https://www.ncbi.nlm.nih.gov/pubmed/37138283 http://dx.doi.org/10.1186/s12967-023-04125-3 |
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author | Guo, Ting Chen, Manli Liu, Ji Wei, Zengyu Yuan, Jinjin Wu, Wenwen Wu, Zhiyun Lai, Yongxing Zhao, Zijun Chen, Hongbin Liu, Nan |
author_facet | Guo, Ting Chen, Manli Liu, Ji Wei, Zengyu Yuan, Jinjin Wu, Wenwen Wu, Zhiyun Lai, Yongxing Zhao, Zijun Chen, Hongbin Liu, Nan |
author_sort | Guo, Ting |
collection | PubMed |
description | OBJECTIVES: Available literature documents that ischemic stroke can disrupt the morphology and function of mitochondria and that the latter in other disease models can be preserved by neuropilin-1 (NRP-1) via oxidative stress suppression. However, whether NRP-1 can repair mitochondrial structure and promote functional recovery after cerebral ischemia is still unknown. This study tackled this very issue and explored the underlying mechanism. METHODS: Adeno-associated viral (AAV)-NRP-1 was stereotaxically inoculated into the cortex and ipsilateral striatum posterior of adult male Sprague-Dawley (SD) rats before a 90-min transient middle cerebral artery occlusion (tMCAO) and subsequent reperfusion. Lentivirus (LV)-NRP-1 was transfected into rat primary cortical neuronal cultures before a 2-h oxygen-glucose deprivation and reoxygenation (OGD/R) injury to neurons. The expression and function of NRP-1 and its specific protective mechanism were investigated by Western Blot, immunofluorescence staining, flow cytometry, magnetic resonance imaging, transmission electron microscopy, etc. The binding was detected by molecular docking and molecular dynamics simulation. RESULTS: Both in vitro and in vivo models of cerebral ischemia/reperfusion (I/R) injury presented a sharp increase in NRP-1 expression. The expression of AAV-NRP-1 markedly ameliorated the cerebral I/R-induced damage to the motor function and restored the mitochondrial morphology. The expression of LV-NRP-1 alleviated mitochondrial oxidative stress and bioenergetic deficits. AAV-NRP-1 and LV-NRP-1 treatments increased the wingless integration (Wnt)-associated signals and β-catenin nuclear localization. The protective effects of NRP-1 were reversed by the administration of XAV-939. CONCLUSIONS: NRP-1 can produce neuroprotective effects against I/R injury to the brain by activating the Wnt/β-catenin signaling pathway and promoting mitochondrial structural repair and functional recovery, which may serve as a promising candidate target in treating ischemic stroke. |
format | Online Article Text |
id | pubmed-10155168 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-101551682023-05-04 Neuropilin-1 promotes mitochondrial structural repair and functional recovery in rats with cerebral ischemia Guo, Ting Chen, Manli Liu, Ji Wei, Zengyu Yuan, Jinjin Wu, Wenwen Wu, Zhiyun Lai, Yongxing Zhao, Zijun Chen, Hongbin Liu, Nan J Transl Med Research OBJECTIVES: Available literature documents that ischemic stroke can disrupt the morphology and function of mitochondria and that the latter in other disease models can be preserved by neuropilin-1 (NRP-1) via oxidative stress suppression. However, whether NRP-1 can repair mitochondrial structure and promote functional recovery after cerebral ischemia is still unknown. This study tackled this very issue and explored the underlying mechanism. METHODS: Adeno-associated viral (AAV)-NRP-1 was stereotaxically inoculated into the cortex and ipsilateral striatum posterior of adult male Sprague-Dawley (SD) rats before a 90-min transient middle cerebral artery occlusion (tMCAO) and subsequent reperfusion. Lentivirus (LV)-NRP-1 was transfected into rat primary cortical neuronal cultures before a 2-h oxygen-glucose deprivation and reoxygenation (OGD/R) injury to neurons. The expression and function of NRP-1 and its specific protective mechanism were investigated by Western Blot, immunofluorescence staining, flow cytometry, magnetic resonance imaging, transmission electron microscopy, etc. The binding was detected by molecular docking and molecular dynamics simulation. RESULTS: Both in vitro and in vivo models of cerebral ischemia/reperfusion (I/R) injury presented a sharp increase in NRP-1 expression. The expression of AAV-NRP-1 markedly ameliorated the cerebral I/R-induced damage to the motor function and restored the mitochondrial morphology. The expression of LV-NRP-1 alleviated mitochondrial oxidative stress and bioenergetic deficits. AAV-NRP-1 and LV-NRP-1 treatments increased the wingless integration (Wnt)-associated signals and β-catenin nuclear localization. The protective effects of NRP-1 were reversed by the administration of XAV-939. CONCLUSIONS: NRP-1 can produce neuroprotective effects against I/R injury to the brain by activating the Wnt/β-catenin signaling pathway and promoting mitochondrial structural repair and functional recovery, which may serve as a promising candidate target in treating ischemic stroke. BioMed Central 2023-05-03 /pmc/articles/PMC10155168/ /pubmed/37138283 http://dx.doi.org/10.1186/s12967-023-04125-3 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Guo, Ting Chen, Manli Liu, Ji Wei, Zengyu Yuan, Jinjin Wu, Wenwen Wu, Zhiyun Lai, Yongxing Zhao, Zijun Chen, Hongbin Liu, Nan Neuropilin-1 promotes mitochondrial structural repair and functional recovery in rats with cerebral ischemia |
title | Neuropilin-1 promotes mitochondrial structural repair and functional recovery in rats with cerebral ischemia |
title_full | Neuropilin-1 promotes mitochondrial structural repair and functional recovery in rats with cerebral ischemia |
title_fullStr | Neuropilin-1 promotes mitochondrial structural repair and functional recovery in rats with cerebral ischemia |
title_full_unstemmed | Neuropilin-1 promotes mitochondrial structural repair and functional recovery in rats with cerebral ischemia |
title_short | Neuropilin-1 promotes mitochondrial structural repair and functional recovery in rats with cerebral ischemia |
title_sort | neuropilin-1 promotes mitochondrial structural repair and functional recovery in rats with cerebral ischemia |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10155168/ https://www.ncbi.nlm.nih.gov/pubmed/37138283 http://dx.doi.org/10.1186/s12967-023-04125-3 |
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