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Mitochondria dysregulation contributes to secondary neurodegeneration progression post-contusion injury in human 3D in vitro triculture brain tissue model

Traumatic Brain injury-induced disturbances in mitochondrial fission-and-fusion dynamics have been linked to the onset and propagation of neuroinflammation and neurodegeneration. However, cell-type-specific contributions and crosstalk between neurons, microglia, and astrocytes in mitochondria-driven...

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Autores principales: Liaudanskaya, Volha, Fiore, Nicholas J., Zhang, Yang, Milton, Yuka, Kelly, Marilyn F., Coe, Marly, Barreiro, Ariana, Rose, Victoria K., Shapiro, Matthew R., Mullis, Adam S., Shevzov-Zebrun, Anna, Blurton-Jones, Mathew, Whalen, Michael J., Symes, Aviva J., Georgakoudi, Irene, Nieland, Thomas J. F., Kaplan, David L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10400598/
https://www.ncbi.nlm.nih.gov/pubmed/37537168
http://dx.doi.org/10.1038/s41419-023-05980-0
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author Liaudanskaya, Volha
Fiore, Nicholas J.
Zhang, Yang
Milton, Yuka
Kelly, Marilyn F.
Coe, Marly
Barreiro, Ariana
Rose, Victoria K.
Shapiro, Matthew R.
Mullis, Adam S.
Shevzov-Zebrun, Anna
Blurton-Jones, Mathew
Whalen, Michael J.
Symes, Aviva J.
Georgakoudi, Irene
Nieland, Thomas J. F.
Kaplan, David L.
author_facet Liaudanskaya, Volha
Fiore, Nicholas J.
Zhang, Yang
Milton, Yuka
Kelly, Marilyn F.
Coe, Marly
Barreiro, Ariana
Rose, Victoria K.
Shapiro, Matthew R.
Mullis, Adam S.
Shevzov-Zebrun, Anna
Blurton-Jones, Mathew
Whalen, Michael J.
Symes, Aviva J.
Georgakoudi, Irene
Nieland, Thomas J. F.
Kaplan, David L.
author_sort Liaudanskaya, Volha
collection PubMed
description Traumatic Brain injury-induced disturbances in mitochondrial fission-and-fusion dynamics have been linked to the onset and propagation of neuroinflammation and neurodegeneration. However, cell-type-specific contributions and crosstalk between neurons, microglia, and astrocytes in mitochondria-driven neurodegeneration after brain injury remain undefined. We developed a human three-dimensional in vitro triculture tissue model of a contusion injury composed of neurons, microglia, and astrocytes and examined the contributions of mitochondrial dysregulation to neuroinflammation and progression of injury-induced neurodegeneration. Pharmacological studies presented here suggest that fragmented mitochondria released by microglia are a key contributor to secondary neuronal damage progression after contusion injury, a pathway that requires astrocyte-microglia crosstalk. Controlling mitochondrial dysfunction thus offers an exciting option for developing therapies for TBI patients.
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spelling pubmed-104005982023-08-05 Mitochondria dysregulation contributes to secondary neurodegeneration progression post-contusion injury in human 3D in vitro triculture brain tissue model Liaudanskaya, Volha Fiore, Nicholas J. Zhang, Yang Milton, Yuka Kelly, Marilyn F. Coe, Marly Barreiro, Ariana Rose, Victoria K. Shapiro, Matthew R. Mullis, Adam S. Shevzov-Zebrun, Anna Blurton-Jones, Mathew Whalen, Michael J. Symes, Aviva J. Georgakoudi, Irene Nieland, Thomas J. F. Kaplan, David L. Cell Death Dis Article Traumatic Brain injury-induced disturbances in mitochondrial fission-and-fusion dynamics have been linked to the onset and propagation of neuroinflammation and neurodegeneration. However, cell-type-specific contributions and crosstalk between neurons, microglia, and astrocytes in mitochondria-driven neurodegeneration after brain injury remain undefined. We developed a human three-dimensional in vitro triculture tissue model of a contusion injury composed of neurons, microglia, and astrocytes and examined the contributions of mitochondrial dysregulation to neuroinflammation and progression of injury-induced neurodegeneration. Pharmacological studies presented here suggest that fragmented mitochondria released by microglia are a key contributor to secondary neuronal damage progression after contusion injury, a pathway that requires astrocyte-microglia crosstalk. Controlling mitochondrial dysfunction thus offers an exciting option for developing therapies for TBI patients. Nature Publishing Group UK 2023-08-03 /pmc/articles/PMC10400598/ /pubmed/37537168 http://dx.doi.org/10.1038/s41419-023-05980-0 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Liaudanskaya, Volha
Fiore, Nicholas J.
Zhang, Yang
Milton, Yuka
Kelly, Marilyn F.
Coe, Marly
Barreiro, Ariana
Rose, Victoria K.
Shapiro, Matthew R.
Mullis, Adam S.
Shevzov-Zebrun, Anna
Blurton-Jones, Mathew
Whalen, Michael J.
Symes, Aviva J.
Georgakoudi, Irene
Nieland, Thomas J. F.
Kaplan, David L.
Mitochondria dysregulation contributes to secondary neurodegeneration progression post-contusion injury in human 3D in vitro triculture brain tissue model
title Mitochondria dysregulation contributes to secondary neurodegeneration progression post-contusion injury in human 3D in vitro triculture brain tissue model
title_full Mitochondria dysregulation contributes to secondary neurodegeneration progression post-contusion injury in human 3D in vitro triculture brain tissue model
title_fullStr Mitochondria dysregulation contributes to secondary neurodegeneration progression post-contusion injury in human 3D in vitro triculture brain tissue model
title_full_unstemmed Mitochondria dysregulation contributes to secondary neurodegeneration progression post-contusion injury in human 3D in vitro triculture brain tissue model
title_short Mitochondria dysregulation contributes to secondary neurodegeneration progression post-contusion injury in human 3D in vitro triculture brain tissue model
title_sort mitochondria dysregulation contributes to secondary neurodegeneration progression post-contusion injury in human 3d in vitro triculture brain tissue model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10400598/
https://www.ncbi.nlm.nih.gov/pubmed/37537168
http://dx.doi.org/10.1038/s41419-023-05980-0
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