SCIENTISTS EXAMINING WITHDRAWAL responses in millimeter-long roundworms have found that a previously dismissed genetic mechanism may contribute to nicotine dependence.

Caenorhabditis elegans roundworms get hooked on nicotine just like humans.

Researchers at the University of Michigan Life Sciences Institute identified specific genes and microRNA that play an essential role in how the roundworms develop nicotine dependence and their withdrawal responses.

These clues may carry over to the mammalian realm. Scientists previously demonstrated that the worms exhibit behavioral responses to nicotine similar to what mammals experience, and that some of the genes involved in nicotine dependence in worms are conserved in mammals – meaning the worms are a good genetic and behavioral model for studying nicotine dependence.

The study took a fresh look at a previously dismissed biological mechanism. Most research in the field has focused on how proteins called nicotine acetylcholine receptors contribute to dependence.

Scientists in the lab of Shawn Xu focused on an earlier step in the genetic coding process and discovered that a series of genes were involved in a process that ultimately increased the production of the nicotine receptor proteins, with microRNAs -a class of small RNA molecules that help fine-tune gene expression – playing a pivotal role.

A researcher in Shaun Xu’s lab and one of the lead authors on the study, Jianke Gong said:

We’re seeing a clear link between nicotine, microRNA, the receptor proteins, and nicotine-dependent behavior.

This mechanism had been dismissed as unimportant to nicotine dependence. However, Xu pointed out, those conclusions were made decades ago, using less sophisticated techniques.

“People believed this question had been settled,” said Xu, a professor at the LSI and in the Department of Molecular and Integrative Physiology at the U-M Medical School.

But we have better tools now. We, as a field, need to take another look at this mechanism in nicotine addiction.

Xu hopes that this latest discovery in C. elegans will now lead other scientists to re-examine the role of these microRNAs in nicotine dependence in mammals, and ultimately lead to a better understanding of what causes the dependence.

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