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Published on: April 15, 2015
SWI/SNF complexes modulate gene expression and the development of physical dependence to ethanol.
Laura D Mathies1,2, GinaMari G Blackwell1, Andrew G Davies1,2
1Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia, USA.
Ethanol dependence in C. elegans causes withdrawal behaviors like WIB. The SWI/SNF complex and gene expression changes, particularly in fatty acid metabolism, mediate this transient dependence.
Area of Science:
- Neuroscience
- Genetics
- Molecular Biology
Background:
- Ethanol (alcohol) exposure can lead to physical dependence and withdrawal symptoms.
- Investigating the genetic and molecular underpinnings of ethanol dependence is crucial for understanding addiction.
- Caenorhabditis elegans (C. elegans) offers a rapid model for studying ethanol-induced changes.
Purpose of the Study:
- To identify ethanol-induced transcriptional changes associated with physical dependence and withdrawal in C. elegans.
- To explore the role of the SWI/SNF chromatin remodeling complex in ethanol withdrawal.
- To elucidate molecular mechanisms underlying transient ethanol dependence.
Main Methods:
- C. elegans were exposed to ethanol for 18 hours to induce physical dependence.
- Withdrawal-induced bordering (WIB), a behavioral change, was observed upon ethanol removal.
- Transcriptional analysis was performed to identify differentially expressed genes correlating with WIB.
Main Results:
- Withdrawal-induced bordering (WIB) is a transient behavior, resolving within 6 hours.
- 1870 genes showed differential expression immediately after ethanol exposure, potentially mediating WIB.
- The SWI/SNF chromatin remodeling complex, specifically swsn-9, is required for normal WIB, indicating both dependent and independent components.
Conclusions:
- Extended ethanol exposure induces transient physical dependence in C. elegans, involving the SWI/SNF complex.
- Genes related to fatty acid metabolism and dod-24 are implicated in ethanol withdrawal.
- Modulation of lipid membrane composition is suggested as a mechanism for ethanol dependence.
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