Age-Dependent Decline in Neuron Growth Potential and Mitochondria Functions in Cortical Neurons

The age of incidence of spinal cord injury (SCI) and the average age of people living with SCI is continuously increasing. However, SCI is extensively modeled in young adult animals, hampering translation of research to clinical applications. While there has been significant progress in manipulating...

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Main Authors: Theresa C. Sutherland, Arthur Sefiani, Darijana Horvat, Taylor E. Huntington, Yuanjiu Lei, A. Phillip West, Cédric G. Geoffroy
Format: Article
Language:English
Published: MDPI AG 2021-06-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/10/7/1625
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author Theresa C. Sutherland
Arthur Sefiani
Darijana Horvat
Taylor E. Huntington
Yuanjiu Lei
A. Phillip West
Cédric G. Geoffroy
author_facet Theresa C. Sutherland
Arthur Sefiani
Darijana Horvat
Taylor E. Huntington
Yuanjiu Lei
A. Phillip West
Cédric G. Geoffroy
author_sort Theresa C. Sutherland
collection DOAJ
description The age of incidence of spinal cord injury (SCI) and the average age of people living with SCI is continuously increasing. However, SCI is extensively modeled in young adult animals, hampering translation of research to clinical applications. While there has been significant progress in manipulating axon growth after injury, the impact of aging is still unknown. Mitochondria are essential to successful neurite and axon growth, while aging is associated with a decline in mitochondrial functions. Using isolation and culture of adult cortical neurons, we analyzed mitochondrial changes in 2-, 6-, 12- and 18-month-old mice. We observed reduced neurite growth in older neurons. Older neurons also showed dysfunctional respiration, reduced membrane potential, and altered mitochondrial membrane transport proteins; however, mitochondrial DNA (mtDNA) abundance and cellular ATP were increased. Taken together, these data suggest that dysfunctional mitochondria in older neurons may be associated with the age-dependent reduction in neurite growth. Both normal aging and traumatic injury are associated with mitochondrial dysfunction, posing a challenge for an aging SCI population as the two elements can combine to worsen injury outcomes. The results of this study highlight this as an area of great interest in CNS trauma.
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spelling doaj.art-7efbdcf7952b4e0fb31912d3d2ffd4782023-11-22T02:09:50ZengMDPI AGCells2073-44092021-06-01107162510.3390/cells10071625Age-Dependent Decline in Neuron Growth Potential and Mitochondria Functions in Cortical NeuronsTheresa C. Sutherland0Arthur Sefiani1Darijana Horvat2Taylor E. Huntington3Yuanjiu Lei4A. Phillip West5Cédric G. Geoffroy6Department of Neuroscience and Experimental Therapeutics, Texas A&M Health Science Center, Bryan, TX 77807, USADepartment of Neuroscience and Experimental Therapeutics, Texas A&M Health Science Center, Bryan, TX 77807, USADepartment of Neuroscience and Experimental Therapeutics, Texas A&M Health Science Center, Bryan, TX 77807, USADepartment of Neuroscience and Experimental Therapeutics, Texas A&M Health Science Center, Bryan, TX 77807, USADepartment of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, Bryan, TX 77807, USADepartment of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, Bryan, TX 77807, USADepartment of Neuroscience and Experimental Therapeutics, Texas A&M Health Science Center, Bryan, TX 77807, USAThe age of incidence of spinal cord injury (SCI) and the average age of people living with SCI is continuously increasing. However, SCI is extensively modeled in young adult animals, hampering translation of research to clinical applications. While there has been significant progress in manipulating axon growth after injury, the impact of aging is still unknown. Mitochondria are essential to successful neurite and axon growth, while aging is associated with a decline in mitochondrial functions. Using isolation and culture of adult cortical neurons, we analyzed mitochondrial changes in 2-, 6-, 12- and 18-month-old mice. We observed reduced neurite growth in older neurons. Older neurons also showed dysfunctional respiration, reduced membrane potential, and altered mitochondrial membrane transport proteins; however, mitochondrial DNA (mtDNA) abundance and cellular ATP were increased. Taken together, these data suggest that dysfunctional mitochondria in older neurons may be associated with the age-dependent reduction in neurite growth. Both normal aging and traumatic injury are associated with mitochondrial dysfunction, posing a challenge for an aging SCI population as the two elements can combine to worsen injury outcomes. The results of this study highlight this as an area of great interest in CNS trauma.https://www.mdpi.com/2073-4409/10/7/1625mitochondriaagingneurite growthdysfunctionmitochondrial respirationCNS Injury
spellingShingle Theresa C. Sutherland
Arthur Sefiani
Darijana Horvat
Taylor E. Huntington
Yuanjiu Lei
A. Phillip West
Cédric G. Geoffroy
Age-Dependent Decline in Neuron Growth Potential and Mitochondria Functions in Cortical Neurons
Cells
mitochondria
aging
neurite growth
dysfunction
mitochondrial respiration
CNS Injury
title Age-Dependent Decline in Neuron Growth Potential and Mitochondria Functions in Cortical Neurons
title_full Age-Dependent Decline in Neuron Growth Potential and Mitochondria Functions in Cortical Neurons
title_fullStr Age-Dependent Decline in Neuron Growth Potential and Mitochondria Functions in Cortical Neurons
title_full_unstemmed Age-Dependent Decline in Neuron Growth Potential and Mitochondria Functions in Cortical Neurons
title_short Age-Dependent Decline in Neuron Growth Potential and Mitochondria Functions in Cortical Neurons
title_sort age dependent decline in neuron growth potential and mitochondria functions in cortical neurons
topic mitochondria
aging
neurite growth
dysfunction
mitochondrial respiration
CNS Injury
url https://www.mdpi.com/2073-4409/10/7/1625
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AT yuanjiulei agedependentdeclineinneurongrowthpotentialandmitochondriafunctionsincorticalneurons
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