miR-212 mediates counter-regulation on CRH expression and HPA axis activity in male mice

Abstract

The mechanisms of hypothalamic-pituitary-adrenal (HPA) axis regulation have been studied persistently but still are not elucidated. Considering the emerging roles of microRNA in stress response, we conducted a microRNA microarray in mice hypothalamus to identify the potential role of microRNAs in regulating the HPA axis. In total, 41 microRNAs changed during heat stress in which we found that miR-212 contains a binding sequence with corticotropin-releasing hormone () 3'UTR according to a sequence analysis. We observed that miR-212 expression in the hypothalamus was escalated by repeated heat and restraint stress. By overexpression or inhibition of miR-212 and the dual-luciferase reporter assay, we proved that miR-212 could bind with 3'UTR to regulate its expression in mice hypothalamus primary cells and in the hippocampus neuron cell line HT-22. In addition, we injected miR-212 agomir or antagomir in mice hypothalamus to overexpress or inhibit miR-212, which leads to alterations of CRH expression and HPA axis activity Furthermore, miR-212 and CRH were both transcribed by the cAMP response element-binding protein (CREB). Overexpression and inhibition of miR-212 affect CREB-dependent CRH expression. Taken together, our results suggest an inhibitory role of miR-212 on the HPA axis, which acts in a counter-regulatory manner.

Loss of T cells influences sex differences in stress-related gene expression

“…However, TCRβ−/−δ−/ − and WT mice showed similar stress reactivity as shown by similar peripheral corticosterone responses to RRS. This finding is concordant with the mirrored increases in plasma CORT found in both RAG-1−/− and WT C57Bl/6 mice exposed daily to RRS and cage-switch stress in addition with a host of previous literature that has demonstrated that RRS is associated with a robust elevation of serum of plasma CORT in mice (Klenerova et al, 2018;Marvar et al, 2012;Tang et al, 2017;Kim and Han, 2009).…”

MiR-130a-3p Inhibits PRL Expression and Is Associated With Heat Stress-Induced PRL Reduction

“…This may because that there is no change in the gene expression of POMC in the pituitary, which also occurred in heat stress experiments in rats (50). Additionally, it is indicated that heat stress regulates CRH expression and HPA axis activity by affecting miR-212 (23). In our study, we found that miR-130a-3p inhibited PRL expression.…”

“…Besides, in our work-in-progress research focused on the genome wide analysis of non-coding RNA in pituitaries of normal and heat-stressed sows, heat stress has already been found to affect miR-130a-3p expression as well as PRL expression. Moreover, studies have shown that miRNAs participate in heat stress response (23), and heat stress induces alteration of endocrine hormones (24). Taken together, data above may suggest a potential relationship among miR-130a-3p, PRL and heat stress.…”

Neuritin inhibits astrogliosis to ameliorate diabetic cognitive dysfunction

“…Then, 40 μg of protein was mixed in a buffer (25% glycerol, 2% SDS, 0.01% bromophenol blue, Tris–HCl, pH 6.8) and heated at 100°C for 5 min. The samples were subjected to 10% SDS-PAGE, followed by transfer onto a PVDF membrane (Roche) using the GelDoc XR system (Bio-Rad) ( Tang et al 2017 ). The membrane was washed with Tris-buffered 154 mmol/L NaCl solution with 0.1% Tween 20, and incubated with anti-rabbit neuritin (Abcam, Catalog #64186), GFAP (Abcam, Catalog #ab7260), JAK2 (Abcam, Catalog # ab108596), p-JAK2 (Abcam, Catalog #ab32101), STAT3 (Abcam, Catalog #ab68153), p-STAT3 (Abcam, Catalog #ab76315), or β-actin polyclonal antibody (100 in dilution, Sigma, Catalog #A2103) for 1 h at 25°C, and incubated with peroxidase-conjugated anti-rabbit IgG (1:1000) for 1 h at 25°C.…”