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Effects of Pyruvate Administration on Mitochondrial Enzymes, Neurological Behaviors, and Neurodegeneration after Traumatic Brain Injury
Traumatic brain injury (TBI) is known to increase the susceptibility to various age-related neurodegenerative disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). Although the role of damaged mitochondrial electron transport chain (ETC) in the progression of AD and PD has been id...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
JKL International LLC
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219499/ https://www.ncbi.nlm.nih.gov/pubmed/34221543 http://dx.doi.org/10.14336/AD.2020.1015 |
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author | Ariyannur, Prasanth S Xing, Guoqiang Barry, Erin S Benford, Brandi Grunberg, Neil E Sharma, Pushpa |
author_facet | Ariyannur, Prasanth S Xing, Guoqiang Barry, Erin S Benford, Brandi Grunberg, Neil E Sharma, Pushpa |
author_sort | Ariyannur, Prasanth S |
collection | PubMed |
description | Traumatic brain injury (TBI) is known to increase the susceptibility to various age-related neurodegenerative disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). Although the role of damaged mitochondrial electron transport chain (ETC) in the progression of AD and PD has been identified, its relationship with altered expression of neurodegenerative proteins has not been examined before. This study aimed to investigate 1) how TBI could affect mitochondrial ETC and neurodegeneration in rat brain regions related to behavioral alteration, and 2) if administration of the key mitochondrial substrate pyruvate can improve the outcome of mild TBI (mTBI). In a rat lateral fluid percussion injury model of mTBI, sodium pyruvate in sterile distilled water (1 g/kg body weight) was administered orally daily for 7 days. The protein expression of mitochondrial ETC enzymes, and neurodegeneration proteins in the hippocampus and cerebral cortex and was assessed on Day 7. The hippocampal and cortical expressions of ETC complex I, III, IV, V were significantly and variably impaired following mTBI. Pyruvate treatment altered ETC complex expression, reduced the nitrosyl stress and the MBP expression in the injured brain area, but increased the expression of the glial fibrillary acidic protein (GFAP) and Tau proteins. Pyruvate after mTBI augmented the Rotarod performance but decreased the horizontal and vertical open field locomotion activities and worsened neurobehavioural severity score, indicating a debilitating therapeutic effect on the acute phase of mTBI. These results suggest bidirectional neuroprotective and neurodegenerative modulating effects of pyruvate on TBI-induced alteration in mitochondrial activity and motor behavior. Pyruvate could potentially stimulate the proliferation of astrogliosis, and lactate acidosis, and caution should be exercised when used as a therapy in the acute phase of mTBI. More effective interventions targeted at multiple mechanisms are needed for the prevention and treatment of TBI-induced long-term neurodegeneration. |
format | Online Article Text |
id | pubmed-8219499 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | JKL International LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-82194992021-07-03 Effects of Pyruvate Administration on Mitochondrial Enzymes, Neurological Behaviors, and Neurodegeneration after Traumatic Brain Injury Ariyannur, Prasanth S Xing, Guoqiang Barry, Erin S Benford, Brandi Grunberg, Neil E Sharma, Pushpa Aging Dis Orginal Article Traumatic brain injury (TBI) is known to increase the susceptibility to various age-related neurodegenerative disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). Although the role of damaged mitochondrial electron transport chain (ETC) in the progression of AD and PD has been identified, its relationship with altered expression of neurodegenerative proteins has not been examined before. This study aimed to investigate 1) how TBI could affect mitochondrial ETC and neurodegeneration in rat brain regions related to behavioral alteration, and 2) if administration of the key mitochondrial substrate pyruvate can improve the outcome of mild TBI (mTBI). In a rat lateral fluid percussion injury model of mTBI, sodium pyruvate in sterile distilled water (1 g/kg body weight) was administered orally daily for 7 days. The protein expression of mitochondrial ETC enzymes, and neurodegeneration proteins in the hippocampus and cerebral cortex and was assessed on Day 7. The hippocampal and cortical expressions of ETC complex I, III, IV, V were significantly and variably impaired following mTBI. Pyruvate treatment altered ETC complex expression, reduced the nitrosyl stress and the MBP expression in the injured brain area, but increased the expression of the glial fibrillary acidic protein (GFAP) and Tau proteins. Pyruvate after mTBI augmented the Rotarod performance but decreased the horizontal and vertical open field locomotion activities and worsened neurobehavioural severity score, indicating a debilitating therapeutic effect on the acute phase of mTBI. These results suggest bidirectional neuroprotective and neurodegenerative modulating effects of pyruvate on TBI-induced alteration in mitochondrial activity and motor behavior. Pyruvate could potentially stimulate the proliferation of astrogliosis, and lactate acidosis, and caution should be exercised when used as a therapy in the acute phase of mTBI. More effective interventions targeted at multiple mechanisms are needed for the prevention and treatment of TBI-induced long-term neurodegeneration. JKL International LLC 2021-07-01 /pmc/articles/PMC8219499/ /pubmed/34221543 http://dx.doi.org/10.14336/AD.2020.1015 Text en copyright: © 2021 Ariyannur et al. https://creativecommons.org/licenses/by/2.0/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 that the original work is properly attributed. |
spellingShingle | Orginal Article Ariyannur, Prasanth S Xing, Guoqiang Barry, Erin S Benford, Brandi Grunberg, Neil E Sharma, Pushpa Effects of Pyruvate Administration on Mitochondrial Enzymes, Neurological Behaviors, and Neurodegeneration after Traumatic Brain Injury |
title | Effects of Pyruvate Administration on Mitochondrial Enzymes, Neurological Behaviors, and Neurodegeneration after Traumatic Brain Injury |
title_full | Effects of Pyruvate Administration on Mitochondrial Enzymes, Neurological Behaviors, and Neurodegeneration after Traumatic Brain Injury |
title_fullStr | Effects of Pyruvate Administration on Mitochondrial Enzymes, Neurological Behaviors, and Neurodegeneration after Traumatic Brain Injury |
title_full_unstemmed | Effects of Pyruvate Administration on Mitochondrial Enzymes, Neurological Behaviors, and Neurodegeneration after Traumatic Brain Injury |
title_short | Effects of Pyruvate Administration on Mitochondrial Enzymes, Neurological Behaviors, and Neurodegeneration after Traumatic Brain Injury |
title_sort | effects of pyruvate administration on mitochondrial enzymes, neurological behaviors, and neurodegeneration after traumatic brain injury |
topic | Orginal Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219499/ https://www.ncbi.nlm.nih.gov/pubmed/34221543 http://dx.doi.org/10.14336/AD.2020.1015 |
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