Exercise May Offset Drinking’s Harmful Epigenetic Effect on the Brain

Drinking alcohol on a regular basis, even in moderation, can cause damage to the brain. Physical activity, however, has been reported to protect cognitive function. So, could exercise counteract drinking’s harmful effects on the brain?

In a recent study conducted at the University of Louisville School of Medicine in Louisville, KY, a group of researchers decided to tackle this question by taking an epigenetic look at how alcohol and exercise affect the brain. Specifically, they looked at alcohol-induced epigenetic and molecular changes that cause cerebrovascular dysfunction, and whether or not physical activity produced any neutralizing effects. Their results were published in the March issue of Scientific Reports.

Over the years, there’s been mixed reviews regarding alcohol. Some studies say that moderate consumption is safe and may even offer some benefits. But not all reports on drinking are favorable. In fact, more studies find that alcohol, especially in excess of the recommended amounts, actually increases the risk of health problems like cancer, liver disease, dementia, and many others.

Even so, the evidence that alcohol does more harm than good doesn’t seem to deter people from drinking. Alcohol use and abuse are on the rise despite efforts to increase awareness. Although there are some effective treatments available for alcoholism, the concern remains on how to prevent and minimize any health risks associated with it.

In recent years, we’ve discovered that many illnesses, behaviors, and other health conditions have some level of epigenetic mechanism at play. We’ve also found that not all epigenetic modifications are permanent. For instance, DNA methylation which adds a methyl group to a molecule hindering gene expression is reversible via DNA demethylation (the removal of a methyl group). Thus, if we can identify the underlying mechanisms implicated in a disorder and determine what factors or environmental influences drive them, perhaps we can then develop better ways to prevent, improve, or even reverse the condition.

In this study, the researchers hypothesized that exercise, an established therapy for neurodegenerative diseases, might prove beneficial to the brain on a molecular level and possibly offset the damages of heavy drinking. Because chronic alcohol use has been linked to brain shrinkage and dementia, the team decided to examine certain chemical reactions associated with these conditions and assess the epigenetic events involved – in particular they measured DNA methyltransferase (DNMT) activity.

Testing on mice, they demonstrated that excessive alcohol intake generated unusually high levels of homocysteine (Hcy) in the blood, a factor associated with cognitive impairment, vascular dementia, and Alzheimer’s disease. This also triggered oxidative stress and elevated endoplasmic reticulum (ER) stress, both characteristics of cellular disruption. In addition, a decrease was found in Hcy metabolism enzymes and cellular hydrogen sulfide (H₂S) levels which are protective against neurodegeneration.

In a mechanistic analysis, it was revealed that alcohol increased epigenetic DNA hypomethylation of the Hcy-induced ER protein (Herp) promoter. Dysfunction in blood-brain-barrier (BBB), a membrane that regulates molecular exchange between blood and brain tissue, and cognitive impairment were also observed in the alcohol-treated mice.

Routine exercise, on the other hand, reversed the alcohol-mediated decrease in DNMT expression. It restored the above mentioned chemical abnormalities and amended vascular permeability and BBB dysfunction. The experimental mice also exhibited significantly improved memory capacity and behavior in comparison to the inactive control group.

Overall, the results of the study indicated that physical activity can correct the adverse effects of drinking due in part by epigenetic alterations. The researchers reported, “Exercise restored Hcy and H₂S to basal levels while ameliorating [alcohol]-induced ER stress, diminishing BBB dysfunction and improving cognitive function via ATF6-Herp-signaling. [Exercise] showed its protective efficacy against [alcohol]-induced neurotoxicity.”

There are so many reasons to exercise and this study only adds to the benefits. As stated by the authors, “Exercise intervention could serve as a powerful preventive and therapeutic approach that can have tremendous improvements [on] physiological function.”

Although this study has positive results, it would be amiss to assume that drinking is ok if you just exercise more. It could help in some ways, but over-consumption of alcohol often leads to many physical and mental health complications. The best way to reduce the risk for alcohol-related diseases is to drink appropriately or not at all.

Source: George AK et al. Exercise Mitigates Alcohol Induced Endoplasmic Reticulum Stress Mediated Cognitive Impairment through ATF6-Herp Signaling. Scientific Reports. 8(1):5158.