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Published on: October 24, 2018
miR-34b attenuates trauma-induced anxiety-like behavior by targeting CRHR1
Jing Zhu1, Zhejun Chen1, Jinxing Tian2
1Department of Integrative Medicine and Neurobiology, State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, Institute of Acupuncture Research, WHO Collaborating Centre for Traditional Medicine, Fudan Institutes of Integrative Medicine, Fudan University, Shanghai 200032, P.R. China.
Abstract:
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 NBI‑27914, a specific corticotropin‑releasing hormone receptor 1 (CRHR1) antagonist. CRHR1 was found to be involved in trauma‑induced anxiety. We then applied bioinformatic analysis to screen microRNAs (miRNAs or miRs) that target CRHR1, and miR‑34b was determined to negatively regulate CRHR1 mRNA in primary hypothalamic neurons. The overexpression of miR‑34b in the paraventricular nucleus (PVN) by a miRNA agomir using a drug delivery system decreased the hyperactivity of the HPA axis and anxiety‑like behavior. Overall, the involvement of the HPA axis in trauma‑induced anxiety was demonstrated, and trauma-induced anxiety was attenuated by decreasing the hyperactivity of the HPA axis via miR‑34b by targeting CRHR1.
