The second approach is to use stem cell-derived neurons to model DNA methylation/gene expression alterations in the brain neurons of AUD subjects. It has been hypothesized that chronic alcohol consumption might result in sustained epigenetic and gene expression alterations in brain neurons, leading to neuroadaptations to alcohol. This hypothesis cannot be tested directly in live human brains. Recent advances in stem cell biology provide a novel opportunity for recapitulating the genetic and epigenetic mechanisms underlying diseases such as AUDs in a culture dish. Excitatory neurons (eg, glutamatergic neurons) and inhibitory neurons (eg, GABAergic neurons), which play a critical role in drug addiction, can be differentiated from human embryonic stem cells (hESCs).101–103 Moreover, stem cell-derived neurons have been demonstrated to be useful in in vitro cellular models to evaluate the function of genetic variants associated with neuropsychiatric disorders (eg, schizophrenia104) and neurodevelopmental disorders (eg, the Rett Syndrome105). With the use of stem cell-derived excitatory or inhibitory neurons as cellular models, we expect to obtain critical information on alcohol consumption-induced epigenomic and transcriptomic changes, thus, mimicking those changes in the brain neurons of AUD subjects.
