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Apelin Deficiency Accelerates the Progression of Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the selective loss of motor neurons. Recent studies have implicated that chronic hypoxia and insufficient vascular endothelial growth factor (VEGF)-dependent neuroprotection may lead to the degeneration of motor neur...

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Autores principales: Kasai, Atsushi, Kinjo, Toshihiko, Ishihara, Rie, Sakai, Ikumi, Ishimaru, Yuki, Yoshioka, Yasuhiro, Yamamuro, Akiko, Ishige, Kumiko, Ito, Yoshihisa, Maeda, Sadaaki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3161091/
https://www.ncbi.nlm.nih.gov/pubmed/21887354
http://dx.doi.org/10.1371/journal.pone.0023968
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author Kasai, Atsushi
Kinjo, Toshihiko
Ishihara, Rie
Sakai, Ikumi
Ishimaru, Yuki
Yoshioka, Yasuhiro
Yamamuro, Akiko
Ishige, Kumiko
Ito, Yoshihisa
Maeda, Sadaaki
author_facet Kasai, Atsushi
Kinjo, Toshihiko
Ishihara, Rie
Sakai, Ikumi
Ishimaru, Yuki
Yoshioka, Yasuhiro
Yamamuro, Akiko
Ishige, Kumiko
Ito, Yoshihisa
Maeda, Sadaaki
author_sort Kasai, Atsushi
collection PubMed
description Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the selective loss of motor neurons. Recent studies have implicated that chronic hypoxia and insufficient vascular endothelial growth factor (VEGF)-dependent neuroprotection may lead to the degeneration of motor neurons in ALS. Expression of apelin, an endogenous ligand for the G protein-coupled receptor APJ, is regulated by hypoxia. In addition, recent reports suggest that apelin protects neurons against glutamate-induced excitotoxicity. Here, we examined whether apelin is an endogenous neuroprotective factor using SOD1(G93A) mouse model of ALS. In mouse CNS tissues, the highest expressions of both apelin and APJ mRNAs were detected in spinal cord. APJ immunoreactivity was observed in neuronal cell bodies located in gray matter of spinal cord. Although apelin mRNA expression in the spinal cord of wild-type mice was not changed from 4 to 18 weeks age, that of SOD1(G93A) mice was reduced along with the paralytic phenotype. In addition, double mutant apelin-deficient and SOD1(G93A) displayed the disease phenotypes earlier than SOD1(G93A) littermates. Immunohistochemical observation revealed that the number of motor neurons was decreased and microglia were activated in the spinal cord of the double mutant mice, indicating that apelin deficiency pathologically accelerated the progression of ALS. Furthermore, we showed that apelin enhanced the protective effect of VEGF on H(2)O(2)-induced neuronal death in primary neurons. These results suggest that apelin/APJ system in the spinal cord has a neuroprotective effect against the pathogenesis of ALS.
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spelling pubmed-31610912011-09-01 Apelin Deficiency Accelerates the Progression of Amyotrophic Lateral Sclerosis Kasai, Atsushi Kinjo, Toshihiko Ishihara, Rie Sakai, Ikumi Ishimaru, Yuki Yoshioka, Yasuhiro Yamamuro, Akiko Ishige, Kumiko Ito, Yoshihisa Maeda, Sadaaki PLoS One Research Article Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the selective loss of motor neurons. Recent studies have implicated that chronic hypoxia and insufficient vascular endothelial growth factor (VEGF)-dependent neuroprotection may lead to the degeneration of motor neurons in ALS. Expression of apelin, an endogenous ligand for the G protein-coupled receptor APJ, is regulated by hypoxia. In addition, recent reports suggest that apelin protects neurons against glutamate-induced excitotoxicity. Here, we examined whether apelin is an endogenous neuroprotective factor using SOD1(G93A) mouse model of ALS. In mouse CNS tissues, the highest expressions of both apelin and APJ mRNAs were detected in spinal cord. APJ immunoreactivity was observed in neuronal cell bodies located in gray matter of spinal cord. Although apelin mRNA expression in the spinal cord of wild-type mice was not changed from 4 to 18 weeks age, that of SOD1(G93A) mice was reduced along with the paralytic phenotype. In addition, double mutant apelin-deficient and SOD1(G93A) displayed the disease phenotypes earlier than SOD1(G93A) littermates. Immunohistochemical observation revealed that the number of motor neurons was decreased and microglia were activated in the spinal cord of the double mutant mice, indicating that apelin deficiency pathologically accelerated the progression of ALS. Furthermore, we showed that apelin enhanced the protective effect of VEGF on H(2)O(2)-induced neuronal death in primary neurons. These results suggest that apelin/APJ system in the spinal cord has a neuroprotective effect against the pathogenesis of ALS. Public Library of Science 2011-08-24 /pmc/articles/PMC3161091/ /pubmed/21887354 http://dx.doi.org/10.1371/journal.pone.0023968 Text en Kasai et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Kasai, Atsushi
Kinjo, Toshihiko
Ishihara, Rie
Sakai, Ikumi
Ishimaru, Yuki
Yoshioka, Yasuhiro
Yamamuro, Akiko
Ishige, Kumiko
Ito, Yoshihisa
Maeda, Sadaaki
Apelin Deficiency Accelerates the Progression of Amyotrophic Lateral Sclerosis
title Apelin Deficiency Accelerates the Progression of Amyotrophic Lateral Sclerosis
title_full Apelin Deficiency Accelerates the Progression of Amyotrophic Lateral Sclerosis
title_fullStr Apelin Deficiency Accelerates the Progression of Amyotrophic Lateral Sclerosis
title_full_unstemmed Apelin Deficiency Accelerates the Progression of Amyotrophic Lateral Sclerosis
title_short Apelin Deficiency Accelerates the Progression of Amyotrophic Lateral Sclerosis
title_sort apelin deficiency accelerates the progression of amyotrophic lateral sclerosis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3161091/
https://www.ncbi.nlm.nih.gov/pubmed/21887354
http://dx.doi.org/10.1371/journal.pone.0023968
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