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Cytosolic dopamine determines hypersensitivity to blunt force trauma [PMD216 EV, cat-1, cat-2]

ABSTRACT: Cytosolic dopamine determines hypersensitivity to blunt force trauma [PMD216 EV, cat-1, cat-2]

PROVIDER: PRJNA1068617 | ENA |

REPOSITORIES: ENA

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Cytosolic dopamine determines hypersensitivity to blunt force trauma [PMD216 EV, cat-1, cat-2]

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

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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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Cytosolic dopamine determines hypersensitivity to blunt force trauma

Project description:This SuperSeries is composed of the SubSeries listed below.

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Project description:Mechanical stress by blunt force trauma elicits a distinct and reproducible transcriptional response in C. elegans. Vhp-1, a MAPK phosphatase, regulates a significant portion of these stress-inducible transcripts.

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Adoptively transferred in vitro-generated MDSCs improve T cell function and antigen-specific immunity after blunt chest trauma-induced lung injury

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A Genomic Score Prognostic of Outcome in Trauma Patients

Project description:Physiological, anatomical, and clinical laboratory analytic scoring systems (APACHE, Injury Severity Score (ISS)) have been utilized, with limited success, to predict outcome following injury. We hypothesized that a peripheral blood leukocyte gene expression score could predict outcome, including multiple organ failure, following severe blunt trauma. Contributor: The Inflammation and the Host Response to Injury Large Scale Collaborative Research Program Keywords: expression profiles cRNA derived from whole blood leukocytes obtained within 12 hours of hospital admission provided gene expression data for the entire genome that were used to create a gene expression score for each patient. Expression profiles from healthy volunteers were averaged to create a reference gene expression profile which was used to compute a difference from reference (DFR) score for each patient. This score described the overall genomic response of patients within the first 12 hours following severe blunt trauma. Regression models were used to compare the association of the DFR, APACHE and ISS scores with outcome.

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