Researchers Isolate Molecular Basis of Alcohol Tolerance

Researchers from UMass Medical School have identified a class of small molecules known as microRNA that may play a crucial role in the development of alcohol tolerance.

Tolerance is the decrease in sensitivity to alcohol that develops with repeated exposures to alcohol over time. Individuals who develop high tolerance (low sensitivity) to alcohol are at increased risk for becoming alcohol dependent.

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"This is an intriguing contribution to efforts aimed at identifying the molecular bases of alcohol tolerance," said NIAAA Director Dr Ting-Kai Li.

In a study led by Steven N. Treistman, PhD, Professor of Psychiatry at the University of Massachusetts Medical School (UMMS), and colleagues at the university's Brudnick Neurospychiatric Research Institute (BNRI), the team found that brain cell membrane structure known as the BK channel develops tolerance to alcohol, particularly in the supraoptic nucleus and the striatum, two brain regions important in alcohol's effects.

The present study led by Dr. Treistman, director of the BNRI, analysed whether microRNA might be involved in the alcohol tolerance observed in the BK channel.

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They found that the amount of a specific microRNA molecule known as miR-9 increases in brain cells within minutes of exposure to alcohol. miR-9 blocks the expression of BK gene variants that contain a specific binding site for the molecule, while sparing those that lack a miR-9 binding site.

The study showed that the BK gene variants were destroyed exhibited high alcohol sensitivity, while those that remained showed significantly lower sensitivity, consistent with the development of tolerance.

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"This represents a novel and elegant mechanism by which neurons are able to adapt to alcohol," said Treistman.

"Moreover, since adaptation, or tolerance, to the drug likely contributes to alcohol abuse, our findings identify a potential molecular target for therapeutic intervention," Treistman added.

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"This study demonstrates for the first time that alcohol exposure can cause rapid changes in microRNA levels, altering gene expression and perhaps behavior," said Antonio Noronha, PhD, director of NIAAA's Division of Neuroscience and Behaviour.

"In future studies, it will be interesting to determine if similar microRNA-based regulatory mechanisms influence alcohol problems in human populations," he added.

Source-ANI
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