Ethanol Metabolism and Osmolarity Modify Behavioral Responses to Ethanol in <i>C. elegans</i>

Alaimo, Joseph T.; Davis, Scott J.; Song, Sam S; Burnette, Christopher R.; Grotewiel, Mike; Shelton, Keith L.; Pierce-Shimomura, Jonathan T.; Davies, Andrew G.; Bettinger, Jill C.

doi:10.1111/j.1530-0277.2012.01799.x

Cited by 61 publications

(96 citation statements)

References 39 publications

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“…Our data fit with the growing body of literature that in zebrafish, as well as C. elegans and fruit flies, the developing embryos do not contain the same tissue concentration of ethanol to which they are exposed (Alaimo et al, 2012; Robinson et al, 2012). This work differs from previously published zebrafish data in that we are examining multiple parameters that have not been previously examined (Table 6).…”

Section: Discussionsupporting

confidence: 88%

Developmental age strengthens barriers to ethanol accumulation in zebrafish

Lovely¹,

Nobles²,

Eberhart³

2014

Alcohol

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Fetal Alcohol Spectrum Disorders (FASD) describes a wide range of phenotypic defects affecting facial and neurological development associated with ethanol teratogenicity. It affects approximately 1 in 100 children born in the United States each year. Genetic predisposition along with timing and dosage of ethanol exposure are critical in understanding the prevalence and variability of FASD. The zebrafish attributes of external fertilization, genetic tractability, and high fecundity make it a powerful tool for FASD studies. However, a lack of consensus of ethanol treatment paradigms has limited the interpretation of these various studies. Here we address this concern by examining ethanol tissue concentrations across timing and genetic background. We utilize headspace gas chromatography to determine ethanol concentration in the AB, fli1:EGFP, and Tu backgrounds. In addition, we treated these embryos with ethanol over two different developmental time windows, 6–24 hours post fertilization (hpf) and 24–48 hpf. Our analysis demonstrates that embryos rapidly equilibrate to a sub-media level of ethanol. Embryos then maintain this level of ethanol for the duration of exposure. The ethanol tissue concentration level is independent of genetic background, but is timing-dependent. Embryos exposed from 6–24 hpf were 2.7–4.2-fold lower than media levels, while embryos were 5.7–6.2-fold lower at 48 hpf. This suggests that embryos strengthen one or more barriers to ethanol as they develop. In addition, both the embryo and, to a lesser extent, the chorion, surrounding the embryo are barriers to ethanol. Overall, this work will help tighten ethanol treatment regimens and strengthen zebrafish as a model of FASD.

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Section: Discussionsupporting

confidence: 88%

Developmental age strengthens barriers to ethanol accumulation in zebrafish

Lovely¹,

Nobles²,

Eberhart³

2014

Alcohol

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“…Ethanol depresses the locomotion speed of wild-type worms, and after 30 min of exposure to ethanol the animals develop acute functional tolerance (AFT). AFT is not caused by increased metabolism or clearance of ethanol (35); instead it is likely to represent physiological compensation for the effects of ethanol in the affected tissues, which include neurons (22,23). In this exposure paradigm, we observe the maximal reduction in speed at 10 min of exposure (35); we refer to this maximal reduction as the initial sensitivity to ethanol.…”

Section: Resultsmentioning

confidence: 87%

SWI/SNF chromatin remodeling regulates alcohol response behaviors in Caenorhabditis elegans and is associated with alcohol dependence in humans

Mathies¹,

Blackwell²,

Austin³

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Alcohol abuse is a widespread and serious problem. Understanding the factors that influence the likelihood of abuse is important for the development of effective therapies. There are both genetic and environmental influences on the development of abuse, but it has been difficult to identify specific liability factors, in part because of both the complex genetic architecture of liability and the influences of environmental stimuli on the expression of that genetic liability. Epigenetic modification of gene expression can underlie both genetic and environmentally sensitive variation in expression, and epigenetic regulation has been implicated in the progression to addiction. Here, we identify a role for the switching defective/sucrose nonfermenting (SWI/SNF) chromatin-remodeling complex in regulating the behavioral response to alcohol in the nematode Caenorhabditis elegans. We found that SWI/SNF components are required in adults for the normal behavioral response to ethanol and that different SWI/SNF complexes regulate different aspects of the acute response to ethanol. We showed that the SWI/SNF subunits SWSN-9 and SWSN-7 are required in neurons and muscle for the development of acute functional tolerance to ethanol. Examination of the members of the SWI/SNF complex for association with a diagnosis of alcohol dependence in a human population identified allelic variation in a member of the SWI/SNF complex, suggesting that variation in the regulation of SWI/SNF targets may influence the propensity to develop abuse disorders. Together, these data strongly implicate the chromatin remodeling associated with SWI/SNF complex members in the behavioral responses to alcohol across phyla.SWI/SNF | alcohol | C. elegans | chromatin remodeling | GWAS

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“…The body wall acts as a barrier to ethanol, and the internal concentration equilibrates at 5-10% of the exogenous ethanol. Behavioral effects are seen at concentrations similar to those that affect humans (Alaimo et al, 2012;Davies et al, 2003).…”

Section: Figure 231 Analysis Of Ethanol-induced Locomotor Behaviors Amentioning

confidence: 89%

“…The severity of the defects is dose dependent (Davis, Li, & Rankin, 2008), and the pathway of ethanol catabolism appears to be conserved between nematodes, flies, and mammals (Alaimo et al, 2012).…”

Section: Studies On Ethanol Toxicitymentioning

confidence: 99%