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

Volha Liaudanskaya; Nicholas J Fiore; Yang Zhang; Yuka Milton; Marilyn F Kelly; Marly Coe; Ariana Barreiro; Victoria K Rose; Matthew R Shapiro; Adam S Mullis; Anna Shevzov-Zebrun; Mathew Blurton-Jones; Michael J Whalen; Aviva J Symes; Irene Georgakoudi; Thomas J F Nieland; David L Kaplan

doi:10.1038/s41419-023-05980-0

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

Volha Liaudanskaya, Nicholas J Fiore, Yang Zhang, Yuka Milton, Marilyn F Kelly, Marly Coe, Ariana Barreiro, Victoria K Rose, Matthew R Shapiro, Adam S Mullis, Anna Shevzov-Zebrun, Mathew Blurton-Jones, Michael J Whalen, Aviva J Symes, Irene Georgakoudi, Thomas J F Nieland, David L Kaplan

Research output: Contribution to journal › Article › peer-review

19 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	496
Journal	Cell Death and Disease
Volume	14
Issue number	8
DOIs	https://doi.org/10.1038/s41419-023-05980-0
State	Published - 3 Aug 2023
Externally published	Yes

Keywords

Humans
Neuroinflammatory Diseases
Inflammation/metabolism
Brain/metabolism
Brain Injuries, Traumatic/metabolism
Contusions/metabolism
Mitochondria/metabolism
Microglia/metabolism
Astrocytes/metabolism

Access to Document

10.1038/s41419-023-05980-0

Cite this

Liaudanskaya, V., Fiore, N. J., Zhang, Y., Milton, Y., Kelly, M. F., Coe, M., Barreiro, A., Rose, V. K., Shapiro, M. R., Mullis, A. S., Shevzov-Zebrun, A., Blurton-Jones, M., Whalen, M. J., Symes, A. J., Georgakoudi, I., Nieland, T. J. F., & Kaplan, D. L. (2023). Mitochondria dysregulation contributes to secondary neurodegeneration progression post-contusion injury in human 3D in vitro triculture brain tissue model. Cell Death and Disease, 14(8), 496. https://doi.org/10.1038/s41419-023-05980-0

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

abstract = "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.",

keywords = "Humans, Neuroinflammatory Diseases, Inflammation/metabolism, Brain/metabolism, Brain Injuries, Traumatic/metabolism, Contusions/metabolism, Mitochondria/metabolism, Microglia/metabolism, Astrocytes/metabolism",

author = "Volha Liaudanskaya and Fiore, {Nicholas J} and Yang Zhang and Yuka Milton and Kelly, {Marilyn F} and Marly Coe and Ariana Barreiro and Rose, {Victoria K} and Shapiro, {Matthew R} and Mullis, {Adam S} and Anna Shevzov-Zebrun and Mathew Blurton-Jones and Whalen, {Michael J} and Symes, {Aviva J} and Irene Georgakoudi and Nieland, {Thomas J F} and Kaplan, {David L}",

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Liaudanskaya, V, Fiore, NJ, Zhang, Y, Milton, Y, Kelly, MF, Coe, M, Barreiro, A, Rose, VK, Shapiro, MR, Mullis, AS, Shevzov-Zebrun, A, Blurton-Jones, M, Whalen, MJ, Symes, AJ, Georgakoudi, I, Nieland, TJF & Kaplan, DL 2023, 'Mitochondria dysregulation contributes to secondary neurodegeneration progression post-contusion injury in human 3D in vitro triculture brain tissue model', Cell Death and Disease, vol. 14, no. 8, pp. 496. https://doi.org/10.1038/s41419-023-05980-0

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T1 - Mitochondria dysregulation contributes to secondary neurodegeneration progression post-contusion injury in human 3D in vitro triculture brain tissue model

AU - Liaudanskaya, Volha

AU - Fiore, Nicholas J

AU - Zhang, Yang

AU - Milton, Yuka

AU - Kelly, Marilyn F

AU - Coe, Marly

AU - Barreiro, Ariana

AU - Rose, Victoria K

AU - Shapiro, Matthew R

AU - Mullis, Adam S

AU - Shevzov-Zebrun, Anna

AU - Blurton-Jones, Mathew

AU - Whalen, Michael J

AU - Symes, Aviva J

AU - Georgakoudi, Irene

AU - Nieland, Thomas J F

AU - Kaplan, David L

PY - 2023/8/3

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N2 - 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.

AB - 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.

KW - Humans

KW - Neuroinflammatory Diseases

KW - Inflammation/metabolism

KW - Brain/metabolism

KW - Brain Injuries, Traumatic/metabolism

KW - Contusions/metabolism

KW - Mitochondria/metabolism

KW - Microglia/metabolism

KW - Astrocytes/metabolism

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DO - 10.1038/s41419-023-05980-0

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JO - Cell Death and Disease

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