Characterization of various histone-modifying enzymes in an animal model of differential emotional temperament
Chaudhury S, Maras PM, Sharma V, Watson SJ, Akil H
Society for Neuroscience. 2017.
Enzymes regulating modified histones are important for the alteration in gene expression in various stress-related conditions including anxiety, depression, and addiction disorders. Of all the enzymes regulating histone modification, histone deacetylases (HDACs) play a critical role in mediating the gene expression patterns in pathophysiology of stress disorders. HDACs are a class of enzymes that remove acetyl groups from core histones (H2A, H2B, H3 and H4), which influences the structure of chromatin and the protein-DNA complex, thereby decreasing the transcription of target genes. Some HDAC inhibitors are currently being used as potential therapeutic targets for a large number of clinical disorders, including psychiatric diseases like depression, anxiety and schizophrenia. Our laboratory has selectively bred lines of high responder (bHR) and low responder (bLR) rats, segregated on the basis of their locomotor exploration of a novel environment. These animals show profound and stable differences in their stress vulnerability and emotional temperament, with bLRs being prone to anxiety-like and depression-like behavior and bHRs being prone to addictive behavior. Here, we evaluate the expression of various HDACs in these lines, both at mRNA and protein levels. We focus on the hippocampus due to its known role in regulating affective behavior, and compare HDAC expression during adulthood, as well as during early postnatal life. These experiments will allow us to characterize the epigenetic signature of the bHR/bLR lines and examine the causative role HDACs play in stress vulnerability-and affective disorders, as well as identify potential targets to modulate these traits.