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

Authors :
Tungtur, Sudheer K.
Wilkins, Heather M.
Rogers, Robert S.
Badawi, Yomna
Sage, Jessica M.
Agbas, Abdulbaki
Jawdat, Omar
Barohn, Richard J.
Swerdlow, Russell H.
Nishimune, Hiroshi
Source :
Scientific Reports; 5/26/2021, Vol. 11 Issue 1, p1-10, 10p
Publication Year :
2021

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) <superscript>G93A</superscript> 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, SOD1<superscript>G93A</superscript> 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 SOD1<superscript>G93A</superscript> mice may reflect the effects on neuroinflammation or bioenergetic stress. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
20452322
Volume :
11
Issue :
1
Database :
Complementary Index
Journal :
Scientific Reports
Publication Type :
Academic Journal
Accession number :
150518860
Full Text :
https://doi.org/10.1038/s41598-021-90438-6