FKBP5 and specific microRNAs via glucocorticoid receptor in the basolateral amygdala involved in the susceptibility to depressive disorder in early adolescent stressed rats

MicroRNA mediators of early life stress vulnerability to depression and suicidal behavior

“…This further corroborates the hypothesis that ELS acts to sensitize the HPA axis to later life stress. In addition, administration of RU486, a non-selective GR antagonist, negated the effects of both ELS and dexamethasone administration across miRNA expression, gene expression, and behavioral measures [73] thereby showing that these effects are dependent on GR signaling. Specifically, RU486 returned rearing, crossing, and grooming behaviors in the open field test, percent time in the open arm of elevated plus maze, and sucrose preference to the same level as controls.…”

“…Other animal models of postnatal ELS are mostly applied in the peri-pubertal time period, near PND-28, in order to approximate teen or adolescent stress. Two independent studies have investigated the effects of chronic variable stress (CVS) on miRNA expression in rodent PFC and basolateral amygdala, respectively [73,74]. Xu et al [73] found that CVS increased miR-18a and −124a expression in the basolateral amygdala by PND-55, but at PND-90, miR-18a expression was the same in CVS and control animals.…”

From feedback loop transitions to biomarkers in the psycho-immune-neuroendocrine network: Detecting the critical transition from health to major depression

“…The miRNA-dependent control of GR and FKBP expression may also be important in MDD, and warrants more extensive interrogation. For example, a miR-124 antagomir counters stressdependent depressive behaviours and activates BNDF , and depressionlike behaviour is associated with increased miR-124a and FKBP5 vs. reduced GR levels in the amygdala (Xu et al, 2017).…”

The role of microRNAs in glucocorticoid action

“…It can be induced by GCs (28,(32)(33)(34), suggesting that it may contribute to negative-feedback regulation of GC sensitivity. In rats (31,34) and mice (32), elevated miR-124-3p levels in the brain were associated with decreased GR levels and GC sensitivity and increased depression-like symptoms. Furthermore, treatment of mice with an miR-124-3p antagonist (antagomir) reduced depression-related behaviors (32).…”

“…Collectively, these findings suggest that miR-124-3p may be both a biomarker and therapeutic target for psychiatric disorders related to dysfunction of the HPA axis. It should be noted that several other putative targets of miR-124 have been identified (37), and miR-124 was reported to influence GR function indirectly via effects on phosphodiesterase 4B (38) or 11␤HSD1 (34).…”