Another approach to investigate transcriptomic changes is based on cultured cell line models. In induced pluripotent stem cell (iPSC)-derived neural cell cultures obtained from healthy individuals and those with AD, significant changes in the expression of the candidate loci GABRA1, GABRG2, and GABRD were observed following 21-day alcohol exposure152. A model based on forebrain neural cells showed a module of 58 co-expressed genes that were uniformly decreased following alcohol exposure153. These alcohol-responsive genes are related to biological functions related to cell cycle, Notch signalling, and cholesterol biosynthesis pathways. An early neural differentiation model showed a wide range of ethanol-mediated transcriptional alterations, including a strong association among modulators involved in protein modification, protein synthesis, and gene expression154. A dopaminergic neuronal model based on SH-SY5Y-differentiated cells showed that cocaine exposure is associated with transcriptomic changes in genes involved in transcription regulation, cell cycle, adhesion, cell projection, mitogen-activated protein kinase, cAMP response element-binding protein, and neurotrophin and neuregulin signalling155. In the same model, cocaine exposure was associated with the down-regulation of several microRNAs, which are involved in post-transcriptional regulation of gene expression in
