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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Main Authors:	Kasai, Atsushi, Kinjo, Toshihiko, Ishihara, Rie, Sakai, Ikumi, Ishimaru, Yuki, Yoshioka, Yasuhiro, Yamamuro, Akiko, Ishige, Kumiko, Ito, Yoshihisa, Maeda, Sadaaki
Format:	Online
Language:	English
Published:	Public Library of Science 2011
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3161091/

id	pubmed-3161091
recordtype	oai_dc
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 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 SOD1G93A 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 SOD1G93A mice was reduced along with the paralytic phenotype. In addition, double mutant apelin-deficient and SOD1G93A displayed the disease phenotypes earlier than SOD1G93A 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 H2O2-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.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Kasai, Atsushi Kinjo, Toshihiko Ishihara, Rie Sakai, Ikumi Ishimaru, Yuki Yoshioka, Yasuhiro Yamamuro, Akiko Ishige, Kumiko Ito, Yoshihisa Maeda, Sadaaki
spellingShingle	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
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
title	Apelin Deficiency Accelerates the Progression of Amyotrophic Lateral Sclerosis
title_short	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_sort	apelin deficiency accelerates the progression of amyotrophic lateral sclerosis
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 SOD1G93A 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 SOD1G93A mice was reduced along with the paralytic phenotype. In addition, double mutant apelin-deficient and SOD1G93A displayed the disease phenotypes earlier than SOD1G93A 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 H2O2-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.
publisher	Public Library of Science
publishDate	2011
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3161091/
_version_	1611472188688302080

Apelin Deficiency Accelerates the Progression of Amyotrophic Lateral Sclerosis

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