Our study using postmortem human brains also found that the magnitude of alcohol-related changes in miRNA levels was constrained over a narrow range of only 20–30%, with only a few miRNAs varying outside of this range (Lewohl et al., 2011). We reason that the small changes detected in miRNA, as well as mRNA expression, in PFC of human alcoholics could be due to an increased expression that is localized to a specific cellular compartment, e.g., the neuronal synapse. Such compartmentalized, enhanced differential expression would become diluted as RNA is extracted from total, unfractionated tissue. Alternatively, a larger differential expression may not be compartment-specific but cell type-specific (e.g., differential expression of immune signaling genes in glial cells or differential expression of neuronal genes in specific neuronal subtypes) and similarly become diluted when RNA is extracted from total tissue containing combined cell subpopulations. Both of these possibilities will be discussed further in the following sections.
