Oxaloacetate treatment preserves motor function in SOD1G93A mice and normalizes select neuroinflammation-related parameters in the spinal cord

Abstract Amyotrophic lateral sclerosis (ALS) remains a devastating motor neuron disease with limited treatment options. Oxaloacetate treatment has a neuroprotective effect in rodent models of seizure and neurodegeneration. Therefore, we treated the ALS model superoxide dismutase 1 (SOD1) G93A mice w...

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Autores principales:	Sudheer K. Tungtur, Heather M. Wilkins, Robert S. Rogers, Yomna Badawi, Jessica M. Sage, Abdulbaki Agbas, Omar Jawdat, Richard J. Barohn, Russell H. Swerdlow, Hiroshi Nishimune
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/38dec4f7c64841b98b4be34960b67c6f
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spelling	oai:doaj.org-article:38dec4f7c64841b98b4be34960b67c6f2021-12-02T16:53:01ZOxaloacetate treatment preserves motor function in SOD1G93A mice and normalizes select neuroinflammation-related parameters in the spinal cord10.1038/s41598-021-90438-62045-2322https://doaj.org/article/38dec4f7c64841b98b4be34960b67c6f2021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90438-6https://doaj.org/toc/2045-2322Abstract Amyotrophic lateral sclerosis (ALS) remains a devastating motor neuron disease with limited treatment options. Oxaloacetate treatment has a neuroprotective effect in rodent models of seizure and neurodegeneration. Therefore, we treated the ALS model superoxide dismutase 1 (SOD1) G93A mice with oxaloacetate and evaluated their neuromuscular function and lifespan. Treatment with oxaloacetate beginning in the presymptomatic stage significantly improved neuromuscular strength measured during the symptomatic stage in the injected mice compared to the non-treated group. Oxaloacetate treatment starting in the symptomatic stage significantly delayed limb paralysis compared with the non-treated group. For lifespan analysis, oxaloacetate treatment did not show a statistically significant positive effect, but the treatment did not shorten the lifespan. Mechanistically, SOD1G93A mice showed increased levels of tumor necrosis factor-α (TNFα) and peroxisome proliferative activated receptor gamma coactivator 1α (PGC-1α) mRNAs in the spinal cord. However, oxaloacetate treatment reverted these abnormal levels to that of wild-type mice. Similarly, the altered expression level of total NF-κB protein returned to that of wild-type mice with oxaloacetate treatment. These results suggest that the beneficial effects of oxaloacetate treatment in SOD1G93A mice may reflect the effects on neuroinflammation or bioenergetic stress.Sudheer K. TungturHeather M. WilkinsRobert S. RogersYomna BadawiJessica M. SageAbdulbaki AgbasOmar JawdatRichard J. BarohnRussell H. SwerdlowHiroshi NishimuneNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sudheer K. Tungtur Heather M. Wilkins Robert S. Rogers Yomna Badawi Jessica M. Sage Abdulbaki Agbas Omar Jawdat Richard J. Barohn Russell H. Swerdlow Hiroshi Nishimune Oxaloacetate treatment preserves motor function in SOD1G93A mice and normalizes select neuroinflammation-related parameters in the spinal cord
description	Abstract Amyotrophic lateral sclerosis (ALS) remains a devastating motor neuron disease with limited treatment options. Oxaloacetate treatment has a neuroprotective effect in rodent models of seizure and neurodegeneration. Therefore, we treated the ALS model superoxide dismutase 1 (SOD1) G93A mice with oxaloacetate and evaluated their neuromuscular function and lifespan. Treatment with oxaloacetate beginning in the presymptomatic stage significantly improved neuromuscular strength measured during the symptomatic stage in the injected mice compared to the non-treated group. Oxaloacetate treatment starting in the symptomatic stage significantly delayed limb paralysis compared with the non-treated group. For lifespan analysis, oxaloacetate treatment did not show a statistically significant positive effect, but the treatment did not shorten the lifespan. Mechanistically, SOD1G93A mice showed increased levels of tumor necrosis factor-α (TNFα) and peroxisome proliferative activated receptor gamma coactivator 1α (PGC-1α) mRNAs in the spinal cord. However, oxaloacetate treatment reverted these abnormal levels to that of wild-type mice. Similarly, the altered expression level of total NF-κB protein returned to that of wild-type mice with oxaloacetate treatment. These results suggest that the beneficial effects of oxaloacetate treatment in SOD1G93A mice may reflect the effects on neuroinflammation or bioenergetic stress.
format	article
author	Sudheer K. Tungtur Heather M. Wilkins Robert S. Rogers Yomna Badawi Jessica M. Sage Abdulbaki Agbas Omar Jawdat Richard J. Barohn Russell H. Swerdlow Hiroshi Nishimune
author_facet	Sudheer K. Tungtur Heather M. Wilkins Robert S. Rogers Yomna Badawi Jessica M. Sage Abdulbaki Agbas Omar Jawdat Richard J. Barohn Russell H. Swerdlow Hiroshi Nishimune
author_sort	Sudheer K. Tungtur
title	Oxaloacetate treatment preserves motor function in SOD1G93A mice and normalizes select neuroinflammation-related parameters in the spinal cord
title_short	Oxaloacetate treatment preserves motor function in SOD1G93A mice and normalizes select neuroinflammation-related parameters in the spinal cord
title_full	Oxaloacetate treatment preserves motor function in SOD1G93A mice and normalizes select neuroinflammation-related parameters in the spinal cord
title_fullStr	Oxaloacetate treatment preserves motor function in SOD1G93A mice and normalizes select neuroinflammation-related parameters in the spinal cord
title_full_unstemmed	Oxaloacetate treatment preserves motor function in SOD1G93A mice and normalizes select neuroinflammation-related parameters in the spinal cord
title_sort	oxaloacetate treatment preserves motor function in sod1g93a mice and normalizes select neuroinflammation-related parameters in the spinal cord
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/38dec4f7c64841b98b4be34960b67c6f
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Oxaloacetate treatment preserves motor function in SOD1G93A mice and normalizes select neuroinflammation-related parameters in the spinal cord

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