In Drosophila, larvae reared on food containing higher levels of ethanol exhibit reduced feeding, dose-dependent developmental delay, reduced survival to adulthood, and reduced adult body size; they also exhibit altered behavioral responses to ethanol as adults, including increased locomotor activation, resistance to the sedating effects, and reduced tolerance development. This system shares multiple characteristics with fetal alcohol spectrum disorders in human.
It has been determined that many of the observed developmental phenotypes can be attributed to ethanol interfering with the insulin signaling pathway in the larval brain, specifically with the expression of insulin-like peptides and insulin receptor (InR). Transgenic overexpression of insulin-like peptides (Ilp5 and Ilp6) in the insulin-producing cells of the larval brain suppresses both the developmental and behavioral abnormalities.
The role of oxidative stress in the observed phenotypes has been investigated, including impact of different expression levels of the antioxidant catalase (Cat).
The roles of the neuropeptide NPF (orthologous to the human NPY gene) and its receptor NPFR have been investigated in relation to the reduction in feeding behavior observed for larvae reared on high levels of ethanol.
Investigations using the Drosophila gene sgg contribute to understanding of how GSK3A/B signaling mediates effects of ethanol. This includes ethanol-induced neuronal apoptosis, which may contribute to the phenotypes of fetal alcohol spectrum disorders.
Animals carrying loss-of-function mutations of Dmtn exhibit sensitivity to developmental ethanol exposure. Wild-type larvae subjected to developmental alcohol exposure exhibit a significant decrease in Dmtn transcript levels.
[updated Jun. 2021 by FlyBase; FBrf0222196]
Alcoholism can be defined as persistence of excessive drinking over a long period of time despite adverse health effects and disruption of social relations (Morozova et al., 2014; pubmed:24395673).
The 2013 Diagnostic and Statistical Manual of Mental Disorders (DSM) combined the two former categorizations of abnormal alcohol use (alcohol abuse and alcohol dependence) into one diagnosis: alcohol use disorder. The severity of an individual's AUD is broken into classifications: mild, moderate, or severe. "Alcoholism" is a non-medical term often used to describe a severe form of alcohol use disorder. (https://www.therecoveryvillage.com/recovery-blog/alcoholism-alcohol-use-disorder-whats-difference/)
Excessive alcohol consumption is associated with increased risk of different types of cancer, higher cardiovascular disease mortality, birth defects, liver diseases, and neuropsychiatric disorders (Morozova et al., 2014; pubmed:24395673).
Alcoholism is a multifactorial, genetically influenced disorder. [from MIM:103780; 2017.12.19]
Fetal Alcohol Spectrum Disorders (FASD) is an umbrella term used to describe the range of birth defects caused by prenatal exposure to ethanol. Ethanol may cause mild to severe damage to the development of an unborn baby, leading to lifelong physical, behavioral, and cognitive disabilities (reviewed in Ehrhart et al. 2018; pubmed:29892052).
