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Cytosolic dopamine determines hypersensitivity to blunt force trauma

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Caenorhabditis elegans

PROVIDER: GSE254142 | GEO | 2024/06/17

REPOSITORIES: GEO

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Cytosolic dopamine determines hypersensitivity to blunt force trauma [N2 injury timeline]

Project description:The selective vulnerability of dopaminergic neurons to trauma-induced neurodegeneration is a conserved phenomenon across species, extending from nematodes to humans. However, the molecular mechanisms contributing to this hypersensitivity to blunt force injury remain poorly understood. We find that dopamine oxidation, a key driver of Parkinson’s Disease, extends its toxic role to the acute challenges of blunt force trauma. Ectopic synthesis of dopamine in serotonergic neurons alone proves sufficient in determining neuronal subtype sensitivity to trauma-induced death. While dopaminergic neurons maintain this neurotransmitter in a functional and benign state, trauma-induced subcellular redox imbalances elicit dopamine-dependent cytotoxicity. Perturbing dopamine synthesis and its packaging into synaptic vesicles further demonstrate how cytosolic dopamine is both necessary and sufficient to drive cell loss upon mechanical stress and during aging. Additionally, trauma activates the B-Zip transcription factor, fos-1, which exacerbates this toxic cascade by transcriptionally upregulating the rate-limiting enzyme in dopamine synthesis, cat-2. In summary, our study unravels the molecular intricacies that render dopaminergic neurons uniquely prone to physical perturbation, highlighting a shared vulnerability across different evolutionary lines.

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Cytosolic dopamine determines hypersensitivity to blunt force trauma

Project description:Cytosolic dopamine determines hypersensitivity to blunt force trauma

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Expression data for C. elegans blunt force trauma

Project description:C. elegans exhibit an age-dependent mechanical stress response to blunt force injury. Stress responses are often defined in part by an elicited cellular transcriptional response. We find in C. elegans that mechanical stress by blunt trauma induces a distinct and age-dependent transcriptional program.

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Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

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