Intermittent hypoxia can aggravate motor neuronal loss and cognitive dysfunction in ALS mice.

<h4>Background</h4>Patients with ALS may be exposed to variable degrees of chronic intermittent hypoxia. However, all previous experimental studies on the effects of hypoxia in ALS have only used a sustained hypoxia model and it is possible that chronic intermittent hypoxia exerts effect...

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Autores principales:	Sung-Min Kim, Heejaung Kim, Jeong-Seon Lee, Kyung Seok Park, Gye Sun Jeon, Jeeheun Shon, Suk-Won Ahn, Seung Hyun Kim, Kyung Min Lee, Jung-Joon Sung, Kwang-Woo Lee
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/363c5f16f13d40f8a7da2dc248d43690
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spelling	oai:doaj.org-article:363c5f16f13d40f8a7da2dc248d436902021-11-18T08:44:32ZIntermittent hypoxia can aggravate motor neuronal loss and cognitive dysfunction in ALS mice.1932-620310.1371/journal.pone.0081808https://doaj.org/article/363c5f16f13d40f8a7da2dc248d436902013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24303073/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Patients with ALS may be exposed to variable degrees of chronic intermittent hypoxia. However, all previous experimental studies on the effects of hypoxia in ALS have only used a sustained hypoxia model and it is possible that chronic intermittent hypoxia exerts effects via a different molecular mechanism from that of sustained hypoxia. No study has yet shown that hypoxia (either chronic intermittent or sustained) can affect the loss of motor neurons or cognitive function in an in vivo model of ALS.<h4>Objective</h4>To evaluate the effects of chronic intermittent hypoxia on motor and cognitive function in ALS mice.<h4>Methods</h4>Sixteen ALS mice and 16 wild-type mice were divided into 2 groups and subjected to either chronic intermittent hypoxia or normoxia for 2 weeks. The effects of chronic intermittent hypoxia on ALS mice were evaluated using the rotarod, Y-maze, and wire-hanging tests. In addition, numbers of motor neurons in the ventral horn of the spinal cord were counted and western blot analyses were performed for markers of oxidative stress and inflammatory pathway activation.<h4>Results</h4>Compared to ALS mice kept in normoxic conditions, ALS mice that experienced chronic intermittent hypoxia had poorer motor learning on the rotarod test, poorer spatial memory on the Y-maze test, shorter wire hanging time, and fewer motor neurons in the ventral spinal cord. Compared to ALS-normoxic and wild-type mice, ALS mice that experienced chronic intermittent hypoxia had higher levels of oxidative stress and inflammation.<h4>Conclusions</h4>Chronic intermittent hypoxia can aggravate motor neuronal death, neuromuscular weakness, and probably cognitive dysfunction in ALS mice. The generation of oxidative stress with activation of inflammatory pathways may be associated with this mechanism. Our study will provide insight into the association of hypoxia with disease progression, and in turn, the rationale for an early non-invasive ventilation treatment in patients with ALS.Sung-Min KimHeejaung KimJeong-Seon LeeKyung Seok ParkGye Sun JeonJeeheun ShonSuk-Won AhnSeung Hyun KimKyung Min LeeJung-Joon SungKwang-Woo LeePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 11, p e81808 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sung-Min Kim Heejaung Kim Jeong-Seon Lee Kyung Seok Park Gye Sun Jeon Jeeheun Shon Suk-Won Ahn Seung Hyun Kim Kyung Min Lee Jung-Joon Sung Kwang-Woo Lee Intermittent hypoxia can aggravate motor neuronal loss and cognitive dysfunction in ALS mice.
description	<h4>Background</h4>Patients with ALS may be exposed to variable degrees of chronic intermittent hypoxia. However, all previous experimental studies on the effects of hypoxia in ALS have only used a sustained hypoxia model and it is possible that chronic intermittent hypoxia exerts effects via a different molecular mechanism from that of sustained hypoxia. No study has yet shown that hypoxia (either chronic intermittent or sustained) can affect the loss of motor neurons or cognitive function in an in vivo model of ALS.<h4>Objective</h4>To evaluate the effects of chronic intermittent hypoxia on motor and cognitive function in ALS mice.<h4>Methods</h4>Sixteen ALS mice and 16 wild-type mice were divided into 2 groups and subjected to either chronic intermittent hypoxia or normoxia for 2 weeks. The effects of chronic intermittent hypoxia on ALS mice were evaluated using the rotarod, Y-maze, and wire-hanging tests. In addition, numbers of motor neurons in the ventral horn of the spinal cord were counted and western blot analyses were performed for markers of oxidative stress and inflammatory pathway activation.<h4>Results</h4>Compared to ALS mice kept in normoxic conditions, ALS mice that experienced chronic intermittent hypoxia had poorer motor learning on the rotarod test, poorer spatial memory on the Y-maze test, shorter wire hanging time, and fewer motor neurons in the ventral spinal cord. Compared to ALS-normoxic and wild-type mice, ALS mice that experienced chronic intermittent hypoxia had higher levels of oxidative stress and inflammation.<h4>Conclusions</h4>Chronic intermittent hypoxia can aggravate motor neuronal death, neuromuscular weakness, and probably cognitive dysfunction in ALS mice. The generation of oxidative stress with activation of inflammatory pathways may be associated with this mechanism. Our study will provide insight into the association of hypoxia with disease progression, and in turn, the rationale for an early non-invasive ventilation treatment in patients with ALS.
format	article
author	Sung-Min Kim Heejaung Kim Jeong-Seon Lee Kyung Seok Park Gye Sun Jeon Jeeheun Shon Suk-Won Ahn Seung Hyun Kim Kyung Min Lee Jung-Joon Sung Kwang-Woo Lee
author_facet	Sung-Min Kim Heejaung Kim Jeong-Seon Lee Kyung Seok Park Gye Sun Jeon Jeeheun Shon Suk-Won Ahn Seung Hyun Kim Kyung Min Lee Jung-Joon Sung Kwang-Woo Lee
author_sort	Sung-Min Kim
title	Intermittent hypoxia can aggravate motor neuronal loss and cognitive dysfunction in ALS mice.
title_short	Intermittent hypoxia can aggravate motor neuronal loss and cognitive dysfunction in ALS mice.
title_full	Intermittent hypoxia can aggravate motor neuronal loss and cognitive dysfunction in ALS mice.
title_fullStr	Intermittent hypoxia can aggravate motor neuronal loss and cognitive dysfunction in ALS mice.
title_full_unstemmed	Intermittent hypoxia can aggravate motor neuronal loss and cognitive dysfunction in ALS mice.
title_sort	intermittent hypoxia can aggravate motor neuronal loss and cognitive dysfunction in als mice.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/363c5f16f13d40f8a7da2dc248d43690
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Intermittent hypoxia can aggravate motor neuronal loss and cognitive dysfunction in ALS mice.

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