Limits...
Amygdalar MicroRNA-15a Is Essential for Coping with Chronic Stress

View Article: PubMed Central - PubMed

ABSTRACT

MicroRNAs are important regulators of gene expression and associated with stress-related psychiatric disorders. Here, we report that exposing mice to chronic stress led to a specific increase in microRNA-15a levels in the amygdala-Ago2 complex and a concomitant reduction in the levels of its predicted target, FKBP51, which is implicated in stress-related psychiatric disorders. Reciprocally, mice expressing reduced levels of amygdalar microRNA-15a following exposure to chronic stress exhibited increased anxiety-like behaviors. In humans, pharmacological activation of the glucocorticoid receptor, as well as exposure to childhood trauma, was associated with increased microRNA-15a levels in peripheral blood. Taken together, our results support an important role for microRNA-15a in stress adaptation and the pathogenesis of stress-related psychopathologies.

No MeSH data available.


Related in: MedlinePlus

FKBP51 Is Regulated by miR-15a In Vitro(A) Schematic illustration of FKBP51 3′ UTR indicating the conserved seed match for miR-15a.(B) Luciferase assay with luciferase fused to the 3′ UTR of FKBP51 containing an intact or a control of a mutated (mut) seed site for miR-15a in the presence of miR-15a or control scramble miR (n = 6) showed a 50% decrease in luciferase levels, t(10) = 9.083, p = 0.000. This decrease was abolished when the intact FKBP51 3′ UTR contained a miR-15a mutated seed. Data are represented as mean ± SEM. ∗∗∗p < 0.001
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC5120368&req=5

fig3: FKBP51 Is Regulated by miR-15a In Vitro(A) Schematic illustration of FKBP51 3′ UTR indicating the conserved seed match for miR-15a.(B) Luciferase assay with luciferase fused to the 3′ UTR of FKBP51 containing an intact or a control of a mutated (mut) seed site for miR-15a in the presence of miR-15a or control scramble miR (n = 6) showed a 50% decrease in luciferase levels, t(10) = 9.083, p = 0.000. This decrease was abolished when the intact FKBP51 3′ UTR contained a miR-15a mutated seed. Data are represented as mean ± SEM. ∗∗∗p < 0.001

Mentions: Consistent with direct targeting of FKBP51 by miR-15a, the seed sequence for miR-15a binding at the 3′ UTR of FKBP51 is highly conserved (Figure 3A). Moreover, a luciferase assay, in which a construct containing luciferase followed by the 3′ UTR of FKBP51 was constructed and transfected into Huh7 cells expressing either miR-15a or a scramble control for it, showed a robust specific reduction in normalized luciferase levels (p < 0.001; Figure 3B). Importantly, this reduction was abolished when the miR-15a seed sequence was mutated (Figure 3B). These results support a regulatory role for miR-15a in directly controlling FKBP51 levels.


Amygdalar MicroRNA-15a Is Essential for Coping with Chronic Stress
FKBP51 Is Regulated by miR-15a In Vitro(A) Schematic illustration of FKBP51 3′ UTR indicating the conserved seed match for miR-15a.(B) Luciferase assay with luciferase fused to the 3′ UTR of FKBP51 containing an intact or a control of a mutated (mut) seed site for miR-15a in the presence of miR-15a or control scramble miR (n = 6) showed a 50% decrease in luciferase levels, t(10) = 9.083, p = 0.000. This decrease was abolished when the intact FKBP51 3′ UTR contained a miR-15a mutated seed. Data are represented as mean ± SEM. ∗∗∗p < 0.001
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5120368&req=5

fig3: FKBP51 Is Regulated by miR-15a In Vitro(A) Schematic illustration of FKBP51 3′ UTR indicating the conserved seed match for miR-15a.(B) Luciferase assay with luciferase fused to the 3′ UTR of FKBP51 containing an intact or a control of a mutated (mut) seed site for miR-15a in the presence of miR-15a or control scramble miR (n = 6) showed a 50% decrease in luciferase levels, t(10) = 9.083, p = 0.000. This decrease was abolished when the intact FKBP51 3′ UTR contained a miR-15a mutated seed. Data are represented as mean ± SEM. ∗∗∗p < 0.001
Mentions: Consistent with direct targeting of FKBP51 by miR-15a, the seed sequence for miR-15a binding at the 3′ UTR of FKBP51 is highly conserved (Figure 3A). Moreover, a luciferase assay, in which a construct containing luciferase followed by the 3′ UTR of FKBP51 was constructed and transfected into Huh7 cells expressing either miR-15a or a scramble control for it, showed a robust specific reduction in normalized luciferase levels (p < 0.001; Figure 3B). Importantly, this reduction was abolished when the miR-15a seed sequence was mutated (Figure 3B). These results support a regulatory role for miR-15a in directly controlling FKBP51 levels.

View Article: PubMed Central - PubMed

ABSTRACT

MicroRNAs are important regulators of gene expression and associated with stress-related psychiatric disorders. Here, we report that exposing mice to&nbsp;chronic stress led to a specific increase in microRNA-15a levels in the amygdala-Ago2 complex and a concomitant reduction in the levels of its predicted target, FKBP51, which is implicated in stress-related psychiatric disorders. Reciprocally, mice expressing reduced levels of amygdalar microRNA-15a following exposure to chronic stress exhibited increased anxiety-like behaviors. In humans, pharmacological activation of the glucocorticoid receptor, as well as exposure to childhood trauma, was associated with increased microRNA-15a levels in peripheral blood. Taken together, our results support an important role for microRNA-15a&nbsp;in stress adaptation and the pathogenesis of stress-related psychopathologies.

No MeSH data available.


Related in: MedlinePlus