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Tungtur 2021 Sci Rep

From Bioblast
Publications in the MiPMap
Tungtur SK, Wilkins HM, Rogers RS, Badawi Y, Sage JM, Agbas A, Jawdat O, Barohn RJ, Swerdlow RH, Nishimune H (2021) Oxaloacetate treatment preserves motor function in SOD1G93A mice and normalizes select neuroinflammation-related parameters in the spinal cord. Sci Rep 11:11051.

» PMID: 34040085 Open Access

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 (2021) Sci Rep

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, SOD1YG93A 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.

Bioblast editor: Reiswig R O2k-Network Lab: US KS Kansas City Swerdlow RH, US KS Kansas City Wilkins H

Labels: MiParea: Respiration, Pharmacology;toxicology  Pathology: Neurodegenerative 

Organism: Mouse  Tissue;cell: Nervous system  Preparation: Isolated mitochondria 

Coupling state: LEAK, OXPHOS, ET  Pathway: N, ROX  HRR: Oxygraph-2k