Abstract 2222 Making a splash: Environmental enrichment has no effect on brain dopamine and serotonin levels or activity in Pekin ducks
Year: 2025
Type: conference-abstract
Abstract: PUFA metabolismTraumatic brain injury (TBI) is one of the most common causes of death worldwide.TBI is categorized into two stages: primary brain injury, which refers to the physical damage sustained at the time of injury, and secondary brain injury, occurring afterward including hypoxemia, hypotension, and inflammation1, leading to cell death and neurodegeneration2.Therefore, attenuating the secondary injury may offer a therapeutic avenue to mitigate the effects of secondary injury.Lipid metabolites play a critical role in regulating neurodegeneration due to their involvement in cell signaling, membrane integrity, and brain function3.One important class of neuroprotective lipids, epoxyeicosatrienoic acids (EETs), reduces inflammation and oxidative stress while promoting vascular dilation and blood flow following TBI.EETs are metabolized by soluble epoxide hydrolase (sEH) into less active dihydroxyeicosatrienoic acids (DHETs), and increased sEH activity after TBI has been associated with heightened inflammation and worse outcomes.Inhibiting sEH has emerged as a potential therapeutic strategy to reduce inflammation.Our studies demonstrated that inhibiting sEH using the pharmaceutical compound 12-(3-Adamantan-1-yl-ureido)dodecanoic Acid (AUDA) reduced neurodegeneration in C. elegans4.Current research explores sEH inhibition post-TBI using both pharmaceutical and genetic approaches in C. elegans.This nematode model is ideal due to its ease of use, simple nervous system, and the fact that 60-80% of its genes are homologous to human genes.AUDA has shown promise in reducing the negative effects of secondary injury.This study investigates the effects of genetic knockout (KO) of sEH on mechanical-induced neurodegeneration by targeting two genes in C. elegans, ceeh-1 and ceeh-2, which are orthologs of the human gene EPHX2.These genes are responsible for epoxide hydrolase activity.Of the two, ceeh-1 is a more potent contributor to sEH activity, making it the primary focus of this study.To assess the effects of genetic sEH inhibition, motor, thrashing, and radial locomotion assays will be used to evaluate the health and recovery of worms following induced TBI.Our results showed that genetic KO of ceeh-1 has substantial effects on mechanical stress-induced neurodegeneration.This research aims to deepen our understanding of the mechanisms driving secondary injury and explore genetic inhibition of sEH as a potential therapeutic strategy for mitigating neurodegeneration and improving recovery after TBI.
Source: Journal of Biological Chemistry
Authors: Nina Wilson, Jenna Schober, Greg Fraley
Institution: Purdue University West Lafayette
Language: English
Subfield: Small Animals
Field: Veterinary
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,430
OpenAlex ID: W4411274427