Alcohol Abuse Leaves Epigenetic Marks in Brain
Alcohol has been found to directly contribute to epigenetic markers in areas of the brain involved in learning and memory. It is therefore possible that stopping epigenetic marker deposition could be a promising therapy to treat alcohol addiction.
Epigenetic markers are chemical modifications on DNA bases that alter the expression of genes without editing the underlying genetic code. One class of epigenetic markers are histone acetylations, the addition of an acetyl group (CH3O) onto the histone proteins that package and protect the DNA.
When alcohol is metabolised by the body it is converted into acetate. Alcohol dosed to mice was isotopically labelled to track its process through the body, which revealed that the acetone derived from alcohol is directly incorporated into histone acetylations in the hippocampus. The hippocampus is the centre of the brain that controls memory and learning. As the enzyme ACSS2 was found to be directly responsible for depositing the alcohol derived acetyl groups on the histones, the results indicate that alcohol related memory formation requires ACSS2.
The National Institute on Drug Abuse (NIAID) estimates that between 40% and 60% of people who have gone through treatment for alcohol addiction will experience relapse. The study authors explain that discovering the role of ACSS2 “is significant because in alcohol use disorders, memory of alcohol-associated cues is a primary driver of craving and relapse, even after prolonged periods of abstinence.” Interfering in the deposition of alcohol derived epigenetic markers could therefore lead to a possible medication to prevent relapses.
The study then assessed the epigenetic impacts of alcohol use in mouse babies in utero. Foetal alcohol syndrome is the disruption of neuronal development resulting from maternal drinking during pregnancy. Symptoms can include any mix of physical defects, intellectual or cognitive disabilities, and problems functioning and coping with daily life. In this study, pregnant mice were dosed with alcohol. It was found that alcohol derived acetyl group were present on the histones of the foetal brains.
The study therefore raises the question if histone acetylation could play a role in other neuropsychiatric disorders.