Electroacupuncture Alleviates Surgical Trauma-Induced Hypothalamus Pituitary Adrenal Axis Hyperactivity Via microRNA-142.

Electroacupuncture (EA) could improve the hyperactivity of the hypothalamus pituitary adrenal (HPA) axis induced by hepatectomy. However, its underlying mechanism still remains largely unclear. Here, we found that hypothalamic corticotrophin releasing hormone (CRH) modulates the function of the HPA axis, while hepatectomy induced an HPA axis disorder and EA application could regulate the hypothalamic CRH. We first demonstrated that microRNAs (miRNAs) target on CRH via bioinformatics analysis and screened them in the primary hypothalamic neurons. MicroR-142 (miR-142) and miR-376c were identified to inhibit CRH at the mRNA and protein levels, and a dual luciferase reporter assay confirmed their binding to the 3'-untranslated regions (3'-UTR) of CRH. Further analyses revealed a decrease in hypothalamic miR-142 expression in the hepatectomy rats and an increase in miR-142 and miR-376c after EA intervention. Importantly, the improvement effect of EA on the HPA axis regulatory function in hepatectomy rats was blocked by miR-142 antagomir. Our findings illustrated that EA could up-regulate hypothalamic miR-142 expression and decrease the CRH level to alleviate the hyperactivity of the HPA axis induced by hepatectomy.

miR-34b attenuates trauma-induced anxiety-like behavior by targeting CRHR1.

Exposure to trauma is a potential contributor to anxiety; however, the molecular mechanisms responsible for trauma-induced anxiety require further clarification. In this study, in an aim to explore these mechanisms, we observed the changes in the hypothalamic pituitary adrenal (HPA) axis using a radioimmunoassay and the changes in anxiety-like behavior using the open field test and elevated plus maze test in a rat model following intervention with NBI­27914, a specific corticotropin­releasing hormone receptor 1 (CRHR1) antagonist. CRHR1 was found to be involved in trauma­induced anxiety. We then applied bioinformatic analysis to screen microRNAs (miRNAs or miRs) that target CRHR1, and miR­34b was determined to negatively regulate CRHR1 mRNA in primary hypothalamic neurons. The overexpression of miR­34b in the paraventricular nucleus (PVN) by a miRNA agomir using a drug delivery system decreased the hyperactivity of the HPA axis and anxiety­like behavior. Overall, the involvement of the HPA axis in trauma­induced anxiety was demonstrated, and trauma-induced anxiety was attenuated by decreasing the hyperactivity of the HPA axis via miR­34b by targeting CRHR1.

Arginine Vasopressin and Arginine Vasopressin Receptor 1b Involved in Electroacupuncture-Attenuated Hypothalamic-Pituitary-Adrenal Axis Hyperactivity in Hepatectomy Rats.

OBJECTIVE: The study aims to know the effect of electroacupuncture (EA) in maintenance of the homeostasis of the neuroendocrine system in hepatectomy rats and the involvement of arginine vasopressin (AVP) signaling in hypothalamus after EA was observed. MATERIALS AND METHODS: Rats were randomly assigned to four groups, including the intact group, model group, sham-EA group, and EA group. EA was given during the perioperative period at the Zusanli (ST36) and Sanyinjiao (SP6) points after hepatectomy. The serum adrenocorticotropic hormone (ACTH) and corticosterone (CORT) levels were detected via radioimmunoassay. The expression of AVP, arginine vasopressin receptor 1a (AVPR1a), arginine vasopressin receptor 1b (AVPR1b), and glucocorticoid receptor (GR) was detected by Western blot after surgery. RESULTS: Compared with the intact group, the ACTH and CORT levels in the serum of model group were increased, whereas the ACTH and CORT levels were decreased in the EA group compared with the model group. Moreover, AVP and AVPR1b protein levels in the pituitary gland were increased in the model group and decreased in the EA group. Further, a distinct increase in the AVP and AVPR1a protein levels was observed in the model group, whereas they were significantly decreased in the EA group. Blockade of AVPR1b by nelivaptan reduced the increase of ACTH and CORT. D [Leu(4) , Lys(8) ] vasopressin can inhibit the effect of EA in rectification of the hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis. CONCLUSIONS: EA application at ST36 and SP6 can ameliorate the hyperactivity of the HPA axis via AVP signaling during the perioperative period.