Glycolytic preconditioning in astrocytes mitigates trauma-induced neurodegeneration.

ABSTRACT: Concussion is associated with a myriad of deleterious immediate and long-term consequences. Yet the molecular mechanisms and genetic targets promoting the selective vulnerability of different neural subtypes to dysfunction and degeneration remain unclear. Translating experimental models of blunt force trauma in C. elegans to concussion in mice, we identify a conserved neuroprotective mechanism in which reduction of mitochondrial electron flux through complex IV suppresses trauma-induced degeneration of the highly vulnerable dopaminergic neurons. Reducing cytochrome C oxidase function elevates mitochondrial-derived reactive oxygen species, which signal through the cytosolic hypoxia inducing transcription factor, Hif1a, to promote hyperphosphorylation and inactivation of the py

SUBMITTER: Solano Fonseca R 

PROVIDER: S-EPMC8448530 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature