Alcohol abuse is an enormous problem causing death and disability to over 43 million people worldwide each year (WHO). Chronic alcohol consumption also contributes to abnormal brain morphology and significant brain volume loss indicative of neurodegeneration. Until there are effective treatments to alter maladaptive behavioral patterns in alcohol abuse, more research is needed to prevent alcohol-induced toxicity and degeneration. We used C. elegans as a model system to identify genetic modulators of alcohol toxicity and explored whether prolonged alcohol exposure damages the nervous system. In our study, we exposed L4-larval stage worms to varying concentrations of ethanol for three days and found a dose-dependent deficit in crawling. Furthermore, we evaluated degeneration by assessing the health of neurons using fluorescent reporters. Compared to the untreated group, we found that ethanol-exposed worms had a significant neurodegeneration. Previous findings using C. elegans have suggested that the innate immune pathway may protect against neurodegeneration caused by drug toxicity (Schreiber & McIntire, 2012). We find that deletion of either the innate immune gene nsy-1 (orthologous to the mammalian ASK-1 MAPKKK) or pmk-1 (orthologous to the mammalian p38 MAPK) caused hypersensitivity to ethanol toxicity. Conversely, boosting innate immune signaling via gain-of-function mutation in nsy-1 produced resistance to ethanol toxicity and ameliorated ethanol-induced cholinergic degeneration. Our findings indicate that prolonged exposure to ethanol leads to both behavioral impairments and neuronal degeneration in C. elegans and that the ASK1/p38 MAP kinase pathway may play a role in ethanol-induced damage to the nervous system. / text
| Identifer | oai:union.ndltd.org:UTEXAS/oai:repositories.lib.utexas.edu:2152/22500 |
| Date | 02 December 2013 |
| Creators | Gomez, Lina Maria |
| Source Sets | University of Texas |
| Language | en_US |
| Detected Language | English |
| Format | application/pdf |
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