We found that AUD leads to a marked increase of splicing factor HSPA6 mRNA levels in the superior frontal cortex, basolateral amygdala, and central nucleus of the amygdala. HSPA6 is an inducible member of the family of heat shock proteins. HSPA6 is much less studied compared to other heat shock proteins, likely due to its relatively recent evolutionary emergence, as HSPA6 is present in the human genome but absent in mice and rats. As a result, no animal studies on HSPA6 are available. Studies on human neurons showed that in response to thermal stress HSPA6 targets nuclear speckles31,32. Nuclear speckles are structures enriched in splicing factors and viewed as compartments supplying splicing factors to transcription sites33. When heat shock occurs, nuclear speckles enlarge due to accumulation (“trapping”) of splicing factors34, which is part of transcriptional reprogramming of the stressed cell. One could hypothesize, therefore, that alcohol-induced increase in HSPA6 expression may represent stress-associated cellular response disrupting the normal functioning of nuclear speckles and consequently halting splicing. Of note, HSPA6 is mostly known for its involvement in carcinogenesis. Specifically, increased expression
