Together, these findings

suggest that gene expression pat

Together, these findings

suggest that gene expression patterns after recovery from stress do not reflect Wnt inhibitor review a return to the stress naïve baseline (even when the behaviors have recovered) and chronic stress alters reactivity to future stressors. Studies examining longer recovery periods, as well as how intermittent stress during recovery might alter gene expression will be necessary to answer whether these seemingly lasting changes might eventually reverse or if additional stressors can compound certain changes. These changes in transcriptome reactivity represent one molecular signature for resilience that are themselves likely to be driven by epigenetic changes discussed in the next section.

Importantly, recent evidence has suggested that the in vivo transcriptional changes in response to stress represent a synthesis of multiple cellular pathways, not simply CORT activation of GR-dependent transcription. Chronic stress increases inflammatory tone and this release of cytokines can activate other signaling pathways, such as NF-kB-dependent transcription. Microarray studies have found that glucocorticoid injections produce distinct gene expression profiles from naïve acute stress (Fig. 2B) and that the gene expression response to a glucocorticoid injection changes click here after exposure to chronic stress (Datson et al., 2013; (Gray et al., 2013). In support of these findings, in vitro studies have demonstrated that simultaneous science activation of GR and NF-kB-dependent transcription results in a unique pattern of gene expression that is distinct from the predicted sum of either pathway activated alone (Rao et al., 2011). These findings illustrate that gene expression changes in response to stress are not solely the product of glucocorticoid activity. Increasingly, research into stress resilience is looking beyond GR-dependent transcription in

order to capture the complexity of the cellular response to stress. Functional insights into the ever-changing brain come from studies of epigenetic regulation. The term “epigenetics” now extends beyond its original definition (Waddington, 1942) to include the continuous, seamless interaction between genes and the factors which regulate gene expression over the life course. The core of the genomic response to those environmental factors such as hormones, cytokines and chemokines and other neuromodulators involves modification of histones (Maze et al., 2013), methylation of cytosine residues on DNA, non-coding RNA’s that modify expression of mRNA molecules, and retrotransposon DNA elements (Mehler, 2008).

Leave a Reply

Your email address will not be published. Required fields are marked *

*

You may use these HTML tags and attributes: <a href="" title=""> <abbr title=""> <acronym title=""> <b> <blockquote cite=""> <cite> <code> <del datetime=""> <em> <i> <q cite=""> <strike> <strong>