Ethanol: response and mechanisms in Caenorhabditis elegans

Abstract

The aim of this project is to identify behavioural phenotypes associated with ethanol in C. elegans and potential molecular targets for ethanol that underpin an ethanol response. This will be achieved through a multi-lateral approach using bioinformatics, genetics and neuroscience based methodology.

In accord with previous experiments, behavioural analysis showed that several phenotypes could be used to describe and assess the state of ethanol induced intoxication and dependence over a range of concentrations. C. elegans exhibits an inhibition of locomotion at high ethanol concentrations. This manifests as a reduction in the population that chemotax towards a food reward whilst lower ethanol concentrations show no such reduction in population chemotaxis. There is also a change in locomotion which characterises an ethanol withdrawal; this is a separate response from the intoxicating behaviour seen at higher concentrations. Similar to the response seen in populations, individual worms show a dose dependent reduction in pharyngeal pumping rate. This also shows no significant difference at lower concentrations to their untreated counterparts.

Observations from studying pharyngeal pumping indicate that worms do show a behavioural response at lower ethanol concentrations. Worms placed in an environment with food and ethanol will not exhibit feeding behaviour as control worms do, instead worms disperse away from the food source. This behaviour can be observed at a threshold of around 10mM ethanol. It is unclear how ethanol causes this phenotype. Overall, these data provides new paradigms for assessing low dose effects. These assays will be important for future studies designed to model low dose effects.

With respect to higher doses, ethanol is known to activate cellular and physiological pathways that underpin stress. Here, we have investigated whether the unfolded protein response (UPR) is an important mediator of stress induced by ethanol. Our evidence suggests no clear activation of the UPR by ethanol concentrations that exert behavioural effects. In an attempt to pre-empt genetic data, we initiated a database of genes involved in ethanol responses, which were mapped on to C. elegans and human homologues. These were used to build an ethanol network, which could be used to refine investigations of ethanol-related genes in C. elegans.

More information

Identifiers

ORCID for Lindy Holden-Dye: orcid.org/0000-0002-9704-1217

ORCID for Vincent O'Connor: orcid.org/0000-0003-3185-5709

Catalogue record

Export record