Endocrine Abstracts

It is a well-known observation that glucocorticoid hormones facilitate the storage of stressful, emotional events into memory. How glucocorticoids act in these cognitive processes has still not been completely clarified. Since almost a decade we have been collecting data indicating that memory formation of stressful events involves epigenetic mechanisms coordinating transcriptional processes in dentate gyrus granule neurons. We found that such events evoke the phosphorylation of Serine-10 and the acetylation of Lysine-14 in the N-terminal tails of histone H3 molecules specifically in mature dentate neurons. Corresponding with in vitro findings, this epigenetic response is required for chromatin remodeling enabling the induction of immediate-early genes such as c-Fos specifically in these neurons. Subsequent studies employing a set of pharmacological and gene deletion approaches showed that the phospho-acetylation of histone H3, as well as associated gene expression and memory formation requires concurrent signaling via the glucocorticoid receptor and the NMDA/ERK/MSK (NMDA: N-methyl-D-aspartate; ERK: Extracellular signal-regulated kinase; MSK: mitogen- and stress-activated kinase) pathways. Thus, epigenetic processes regulating induction of gene transcription are involved in neuroplasticity processes in dentate neurons necessary for the formation of memories of the endured event. Glucocorticoid hormones secreted as a result of the stressful event play a critical role as signaling molecules in these epigenetic processes. Possible mechanisms of glucocorticoid action will be discussed.

Supported by the MRC and BBSRC