Breaking the Chains: Advances in Substance Addiction Research through Single-Cell Sequencing, Epigenetics, and Epitranscriptomic

Abstract

Addiction is a complex brain disease influenced by genetic, environmental, and neurological factors. Psychostimulants, cocaine, and methamphetamine influence different cell types in different brain regions, with a focus on the neurons responsible for rewarding effects in the nucleus accumbens (NAc) and ventral tegmental area (VTA). Known markers for psychostimulant-induced neuronal plasticity in combination with droplet-based high-throughput single-cell sequencing divided the heterogeneity of cell populations in NAc and VTA into clusters, where all cells of the same type do not respond equally to exposure to psychostimulants. To explain psychostimulant-induced neuronal plasticity as changes in the amplitude and phase shifts of gene expression, we focused on epigenetic mechanisms of DNA and chromatin modifications, as well as DNA accessibility. We also comment on epitranscriptomics as a novel approach in the study of messenger RNA posttranslational modification, which regulates translation and potentially localized transcription in synapses in order to address the molecular chains that connect addiction from changes in gene expression to synaptic and, finally, neuronal plasticity.