A Cocktail for Gene Alteration

Sleep allows for many restorative functions of the body including regulation of the immune, cardiovascular, and neural system. Due to the increasing demands of the day, individuals are constantly searching for ways to maximize their precious sleep hours. However, chugging 1, 2, 3+ glasses of wine within that short dinner hour is not a good way meet that goal. According to the Center for Disease Control (CDC), binge drinking is a major issue with one in six adults consuming seven alcoholic beverages within a short amount of time each week. Research has shown for several years now that reduced sleep quality is one of the consequences of alcohol consumption; however, the specific mechanisms of this were unknown. Enter Sharma, Sahota, & Thakkar: researchers from the University of Missouri have recently shown that a single binge drinking episode modifies a gene that regulates sleep.

Generally speaking, the body has developed mechanisms to metabolize the delicious and enticing toxin that is ethanol, if ingested slowly. Because of its size and amphipathic nature, it can diffuse freely through the membranes of cells and travel in the blood (Peet, 2012). EtOH is quickly converted to acetaldehyde by alcohol dehydrogenase (ADH – not to be confused with antidiuretic hormone) at the expense of an NAD+ molecule as it is reduced to NADH in the liver. Acetaldehyde is then rapidly converted to acetate by acetaldehyde dehydrogenase (ALDH) at the same time that another NAD+ is reduced (Peet, 2012). Again, this is the normal metabolism of EtOH when it is ingested slowly. However, if large amounts of EtOH are consumed rapidly, the body cannot metabolize the substance quickly enough resulting in an excess amount of EtOH that can travel to and enter the brain (Murty, 2004). In the brain, EtOH is known to act on the glutamate and GABA neurotransmission but it also affects adenosine neurotransmission (Sharma, Engemann, Sahota, & Thakkar, 2010). In this study, Sharma, Sahota, & Thakkar (2018) showed that EtOH acts directly on neurons in the brain (basal forebrain specifically) by downregulating the equilibrative nucleoside transporter-1 (ENT-1), a regulatory gene in the adenosinergic system involved in sleep homeostasis. In their experiment, mice exposed to binge drinking showed reduced expression of ENT-1 mice and a diminished homeostatic sleep response. As we know, disruptions in homeostasis can have multiple metabolic and physiologic implications, explaining the prevalence of sleep disorders in alcoholism.

Ultimately, the authors addressed their hypothesis. They showed that a single episode of binge drinking results in changes to sleep homeostasis through alterations in the gene that regulates sleep. Further studies researching the duration of these changes would be worth investigation to determine if these changes are preserved long-term or potentially reversible. This would shed light into prospective treatment options for sleep disturbances in alcoholism.

References:

Center for Disease Control. (2018). CDC - Fact Sheets-Binge Drinking - Alcohol. Retrieved from https://www.cdc.gov/alcohol/fact-sheets/binge-drinking.htm

Murty, B. R. (2004). The biochemistry of alcohol toxicity. Resonance, 9(10), 41–47. https://doi.org/10.1007/BF02834868

Peet, A. (2012). Metabolism of Ethanol. In S. Rhyner, Marks’ Basic Medical Biochemistry (4th ed., pp. 457-470). Philadelphia, PA: Lippincott Williams & Wilkins.

Sharma, R., Engemann, S. C., Sahota, P., & Thakkar, M. M. (2010). Effects of ethanol on extracellular levels of adenosine in the basal forebrain: an in vivo microdialysis study in freely behaving rats. Alcoholism, Clinical and Experimental Research, 34(5), 813–818. https://doi.org/10.1111/j.1530-0277.2010.01153.x

Sharma, R., Sahota, P., & Thakkar, M. M. (2018). A single episode of binge alcohol drinking causes sleep disturbance, disrupts sleep homeostasis, and down-regulates equilibrative nucleoside transporter 1. Journal of Neurochemistry, 146(3), 304–321. https://doi.org/10.1111/jnc.14470