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

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 ( < 0.01). Rhynchophylline treatment significantly counteracted these changes ( < 0.01). Methamphetamine-induced CPP upregulated 23 miRNAs (log fold change [FC] > 1, < 0.01) in serum exosomes, whereas rhynchophylline treatment could downregulate these miRNAs (log FC < -1, < 0.01). Analysis of hippocampal miRNAs profiles found 22 DE miRNAs (log FC > 1 or <-1, < 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.