Glucocorticoid-induced depression - the role of the dopaminergic system and microRNAs.

Abstract

Presentation of the role of the dopaminergic system and microRNAs in the development of depression after glucocorticoids (GCs) therapy. GCs are steroid hormones secreted by the adrenal glands, and their synthesis is regulated by the hypothalamic-pituitary- adrenal (HPA) axis. The secretion of GCs (cortisol in humans and corticosterone in rodents) is dependent directly on corticotropin, secreted from the pituitary gland and indirectly on the corticotropin-releasing factor, a hormone released from the paraventricular nuclei of the hypothalamus. Prolonged treatment with GCs disrupts the functions of the HPA axis, impairs the dopaminergic system, suppresses hippocampal neurogenesis and sensitizes the amygdala, leading to an increased susceptibility to depression. This is an important problem because GCs are commonly prescribed for a broad range of medical conditions, including inflammatory and autoimmune disorders. The action of GCs may be at least partially regulated by epigenetic mechanisms (microRNAs), in addition to which microRNAs modulate GCs production and cellular response to GCs. The administration of GCs may lead to changes in dopaminergic system activity (e.g. D2 receptors activity), which significantly contribute to the predisposition to depression. Additionally, GCs therapy may cause changes in the activity of micro-RNAs (e.g. miR-124), which exacerbates symptoms of depression. Searching for specific changes in microRNA expression will provide clinically practical and easily applicable biomarkers of depression risk and new forms of pharmacotherapy in GC-induced depression.