The learning and memory disabilities associated with fetal alcohol spectrum disorder (FASD) are due, in part, to hippocampal damage caused by ethanol exposure during prenatal development. However, the mechanism by which alcohol damages the developing hippocampus remains poorly understood. In the current study, researchers examined how ethanol exposure in neonatal rats – a period that is developmentally equivalent to the third trimester of pregnancy in humans -- affects neuronal activities in the hippocampus. They report that in vivo and in vitro ethanol exposure potently inhibits molecular processes that are vital for the proper function and maturation of hippocampal neurons. Most importantly, the ethanol effect reaches significance at concentrations that can be achieved by a pregnant woman consuming less than a single standard drink in an hour. Although many other studies have shown effects of ethanol on synaptic function in developing neurons, the study reported here reveals the most potent effect of ethanol to date. It suggests that even low amounts of alcohol consumption during pregnancy may cause irreversible effects on hippocampal neurons and contribute to FASD.
Binge drinking is common during adolescence, a period of rapid brain development. In this study, researchers used adolescent nonhuman primates to examine the effects of long-term binge alcohol consumption on brain development. They found that an 11-month period of heavy binge alcohol consumption by nonhuman primates led to a significant and persistent reduction in neurogenesis – the birth and maturation of new neurons – in the hippocampus, a brain region involved in learning and memory formation. Alcohol specifically interfered with the division and migration of hippocampal precursor cells. The lasting reduction in hippocampal neurogenesis was paralleled by an increase in neural degeneration. The findings demonstrate that hippocampal development during adolescence is highly vulnerable to alcohol, and suggests that alcohol-induced hippocampal degeneration is one of several factors that may increase the vulnerability to alcohol use disorders.
Brain circuits that connect the frontal lobes with the cerebellum are damaged in chronic alcoholics and may contribute to cognitive deficits in these individuals. But whether these “frontocerebellar” abnormalities are present in individuals at high risk for alcoholism before they start using alcohol is unknown. To find out, scientists led by Dr. Megan Herting at the Oregon Health and Science University conducted brain imaging studies with young people whose positive family history for alcoholism put them at high risk for the disease. Using two different brain imaging techniques -- functional connectivity magnetic resonance imaging and diffusion tensor imaging – the researchers found that family history positive adolescents who had never used alcohol had fewer functional connections between areas of the prefrontal cortex and the cerebellum than did youth with no family history for alcoholism. The researchers also found that the reduction in functional connectivity was associated with reduced white matter structural integrity in other parts of the frontocerebellar circuitry. Taken together, the findings suggest that frontocerebellar abnormalities may be a biological marker of risk for alcohol use disorders.
Episodes of heavy alcohol consumption leading to intoxication are associated with many health and safety problems, including unintentional injuries, sexual assault, domestic violence and alcohol poisoning. Previous studies have shown that brain molecules called GABAA receptors appear to play a role in excessive drinking. In a new study, researchers used an established rat model of binge drinking to investigate how GABAA receptors interact with other brain molecules to influence excessive drinking. The researchers established, for the first time, a direct connection between a molecule known as Toll-like receptor 4 (TLR4) and GABAA receptors. TLR4 is an innate immune system molecule that contributes to the inflammation and brain damage brought on by excessive drinking. Using gene therapy techniques, the researchers targeted TLR4 and GABAA receptors in brains of heavy-drinking rats. They found that silencing the genes for TLR4 and GABAA receptors in certain areas of the brain caused the rats to lose interest in alcohol, an effect that lasted for two weeks after the procedure. The new findings provide exciting new knowledge about the biology of binge drinking in this animal model. It is an important step in understanding brain pathways involved in excessive alcohol consumption and reveals new targets for exploring therapeutic interventions for human drinking.
Alcohol use during pregnancy contributes to many problems in exposed children. Heavy prenatal alcohol exposure leads to fetal alcohol syndrome, a devastating birth defect characterized by craniofacial malformations, neurological and motor deficits, intrauterine growth retardation, learning disabilities, and behavioral and social deficits. Most women who drink alcohol during pregnancy, however, are light-to-moderate drinkers in early pregnancy and quit or decrease their alcohol use by mid-pregnancy. In this long-term study, researchers examined effects of lower levels of prenatal alcohol exposure. They specifically focused on the relation of prenatal alcohol exposure to a subsequent diagnosis of conduct disorder during childhood. Conduct disorder is a pattern of aggressive, destructive, or unlawful behavior problems. The study sample included 592 adolescents and their mothers. Women in the study were interviewed at their fourth and seventh prenatal months, and then at routine intervals post-partum until their children were 16 years old. The researchers found that children who had been exposed to an average of one or more drinks of alcohol per day in the first trimester of pregnancy were three times more likely to meet criteria for a diagnosis of conduct disorder than were adolescents whose mothers drank less than that amount or abstained.