Inhibiting microRNA-137 may be therapeutic for the treatment of alcohol use disorder
Among instances of adolescent binge-drinking, a group of researchers at the University of Illinois at Chicago found that inhibiting microRNA-137 may be an efficient option to treating the progression of alcohol use disorder into adulthood.
The findings, published in the peer-reviewed journal eNeuro, began by identifying the role of microRNA-137 in early binge-drinking among adolescents.
According to Evan Kyzar, co-author of the study: “We investigated the role of microRNA-137 (miR-137), which is crucial for normal neurodevelopment and targets LSD1, in adolescent intermittent ethanol (AIE) exposure-induced anxiety-like and alcohol-drinking behaviors and related epigenetic reprogramming in the amygdala in adulthood.”
As part of the study, researchers examined the effects of binge-drinking in humans by replicating in adolescent rodents, administering alcohol in a cycle of alcohol exposure for two days followed by a short break for two days. This pattern was repeated eight times.
Upon reaching adulthood, researchers conducted tests on behavior and particular brain changes. What the team found was that altered levels of microRNA-137 was linked to altered levels of lysine-specific histone demethylase 1A, or LSD1.
Inhibiting microRNA-137 led to stabilized levels of LSD1 associated with the rodents not exposed to alcohol use during adolescence, the findings indicated. In addition to reduced alcohol use, the inhibition of microRNA-137 also decreased anxiety.
“Adolescent alcohol exposure is a serious public health problem and contributes to alcohol use and anxiety disorders later in life,” wrote Kyzar.
“Inhibition of microRNA-137 in the CeA reverses increased alcohol intake and anxiety-like behavior, and this effect is mediated by lysine-specific demethylase 1 (LSD1), a microRNA-137 target gene that regulates epigenetic programming,” Kyzar added.
“Thus, we have identified microRNA-137 and its target LSD1, in the CeA that play a mechanistic role in the pathogenesis of increased adult anxiety and alcohol consumption after adolescent alcohol exposure.”