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

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.; Kaplan, D. L.

doi:10.1101/2022.09.23.509276

bioRxiv · 10.1101/2022.09.23.509276

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

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.·Kaplan, D. L.

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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 the development of therapies for TBI patients.

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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., Kaplan, D. L.. 2022-09-26. Mitochondria dysregulation contributes to secondary neurodegeneration progression post-contusion injury in human 3D in vitro triculture brain tissue model.. https://doi.org/10.1101/2022.09.23.509276

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