Abstract

This study determined the expression of plasminogen activator inhibitor-1 (PAI-1) and microRNA (miR)-17 in a mouse depression model. Forty male mice were divided evenly into control and depression groups. A chronic unpredictable mild stress (CUMS) model was constructed. qRT-PCR was used to determine the expression of PAI-1 mRNA and miR-17. Western blotting and ELISA were used to determine expression of PAI-1 protein. Dual luciferase reporter assay was carried out to identify direct interaction between miR-17 and PAI-1 mRNA. The mice with depression had elevated PAI-1 mRNA and protein in hippocampal tissues and blood. Expression of miR-17 was decreased in hippocampal tissues and blood from mice with depression. miR-17 bound with the 3′-UTR of PAI-1 mRNA to regulate its expression. This study demonstrated that miR-17 expression in hippocampal tissues and blood from mice with depression was decreased while expression of PAI-1 mRNA and protein was up-regulated. miR-17 participated in depression in mice by regulating PAI-1.

Highlights

  • With the increase of competition pressure in modern society, the number of people suffering from depression is increasing day by day [1,2]

  • The theoretical basis of chronic unpredictable mild stress (CUMS) animal model is similar to the mechanism underlying the occurrence and development of depression caused by chronic and low-level stressors in humans

  • Plasminogen activator inhibitor-1 (PAI-1) is deposited in extracellular matrix, promotes the formation of lipoid and atheromatous plaque, thickens basement membranes, and hardens vessel walls, promoting the occurrence and development of vascular diseases [24]

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Summary

Introduction

With the increase of competition pressure in modern society, the number of people suffering from depression is increasing day by day [1,2]. Decreased hippocampal volume and nerve density are closely associated with depression [3]. Animal experiments confirm the disorder and looseness of the hippocampal neurons in animal models for depression [4]. The nuclei of hippocampal neurons are crinkled, and the nuclear membrane becomes concave-convex [5]. Cerebrovascular lesions have always been an important topic in depression research. The tPA/PAI-1-plasmin system widely exists in the central nervous system of human beings [7], and participates in a variety of molecular mechanisms in the brain [8]. The expression level of PAI-1 in depressed women is higher than that in normal group [9]. A single nucleotide polymorphism in the PAI-1 gene is found to be associated with antidepressant response [10]

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