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

Pharmacology and Molecular Therapeutics

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

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	American English
Journal	Cell Death and Disease
Volume	14
Issue number	8
DOIs	https://doi.org/10.1038/s41419-023-05980-0
State	Published - Jan 2023

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). https://doi.org/10.1038/s41419-023-05980-0

@article{6e31db0f449b432eb631368191ec0556,

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.",

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.}",

year = "2023",

month = jan,

doi = "10.1038/s41419-023-05980-0",

language = "American English",

volume = "14",

journal = "Cell Death and Disease",

issn = "2041-4889",

publisher = "Springer Nature",

number = "8",

}

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. https://doi.org/10.1038/s41419-023-05980-0

TY - JOUR

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 - 2023/1

Y1 - 2023/1

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.

UR - https://www.mendeley.com/catalogue/48adf4b9-015c-3b5f-adb1-2f445f11a7bc/

U2 - 10.1038/s41419-023-05980-0

DO - 10.1038/s41419-023-05980-0

M3 - Article

C2 - 37537168

SN - 2041-4889

VL - 14

JO - Cell Death and Disease

JF - Cell Death and Disease

IS - 8

ER -