Expression of miRNAs in Serum Exosomes versus Hippocampus in Methamphetamine‐Induced Rats and Intervention of Rhynchophylline

Abstract

Objective To compare the expressions of miRNAs (microRNAs) in serum exosomes and in hippocampus and to provide insights into the miRNA-mediated relationship between peripheral and central nervous systems in the presence of methamphetamine. Methods Published results on conditioned place preference (CPP) in rats conditioned by methamphetamine were replicated. The expressions of miRNAs in serum exosomes and hippocampus were determined by gene-chip sequencing. We then predicted the potential target genes of selected, differentially expressed (DE) miRNAs and then carried out functional analysis of these target genes. We also verified our results by RT-qPCR. Results Methamphetamine reward could greatly increase the activity time and distance in the intrinsically nonpreferred side of the behavioral apparatus compared with control rats (P < 0.01). Rhynchophylline treatment significantly counteracted these changes (P < 0.01). Methamphetamine-induced CPP upregulated 23 miRNAs (log2 fold change [FC] > 1, P < 0.01) in serum exosomes, whereas rhynchophylline treatment could downregulate these miRNAs (log2 FC < −1, P < 0.01). Analysis of hippocampal miRNAs profiles found 22 DE miRNAs (log2 FC > 1 or <−1, P < 0.01). When methamphetamine induced CPP, 11 of those miRNAs were upregulated, whereas rhynchophylline treatment could downregulate these miRNAs. The other 11 miRNAs behaved in the opposite way. We selected six DE miRNAs from each of serum exosomes and hippocampus for target gene prediction and functional analysis. We found that, in both, the DE miRNAs and their target genes may be related to neuronal information transmission and synaptic transmission. Conclusions Rhynchophylline blocked the alteration of behavior and the expression of some DE miRNAs induced by methamphetamine. The biological functions of these DE miRNAs target genes are correlated between serum exosomes and hippocampus. As to these biological processes and pathways which are involved in the development of addiction at multiple stages, we speculate that these DE miRNAs in serum exosomes and hippocampus are closely related to methamphetamine addiction.

Methamphetamine use alters human plasma extracellular vesicles and their microRNA cargo: An exploratory study

“…Rodent models have also been used to investigate the effects of MA on miRNA expression in brain and serum EVs (Bosch et al., 2015; Du et al., 2016; Li et al., 2018; Li et al., 2018; Sim et al., 2017; Zhu et al., 2015,). In the rat VTA, miRNAs previously associated with MA addiction (miR‐124 and miR‐181a) as well as novel miRNAs (miR‐125a‐5p and miR‐145) are decreased in expression following 14 days of abstinence (Bosch et al., 2015).…”

Using exosomal miRNAs extracted from porcine follicular fluid to investigate their role in oocyte development

“…Exosomes act as carriers to follicles from the surrounding somatic cells as well as the body and blood to influence oocyte maturation. Moreover, immune stimulus has been shown to enhance vasodilatation to promote exosomal function [ 29 , 30 ]. Past work has also shown that miR-194a family expression plays an important role in immunological responses and function, including the flounder [ 31 ] and zebrafish [ 32 ] immune responses.…”

Research on miRNAs of exosomes’ role on porcine oocyte development by extracted from follicular fluid

“…2. Exosomes is carriers to follicles from surrounding somatic cells body blood to influence oocyte maturation, which immune stimulus could enhance vasodilatation in order to promote EXs function 29,30 . It is also indicated that miR-194a family expression play important roles in immunology response and function, such as flounder immune response 31 and zebrafish 32 .…”