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.
Highlights
IntroductionUncaria rhynchophylla (diao gou teng; literally: “fish hook vine,” or the cat’s claw herb; its Chinese and Japanese name, Gouteng and Chotoko, resp.) is a traditional Chinese medicinal herb
Uncaria rhynchophylla is a traditional Chinese medicinal herb
The movement distance and activity time of rats in nonpreferred compartment was greatly increased by methamphetamine compared with that of the control rats (P < 0.01), whereas rhynchophylline decreased the movement distance and activity time significantly and providing values like those in the control group (P < 0.01)
Summary
Uncaria rhynchophylla (diao gou teng; literally: “fish hook vine,” or the cat’s claw herb; its Chinese and Japanese name, Gouteng and Chotoko, resp.) is a traditional Chinese medicinal herb. Rhynchophylline, a monoamine indole alkaloid, is one of the main effective components of U. rhynchophylla. Rhynchophylline has inhibitory effects on the brain Lcalcium channel, the central glutamate system, and the cardiovascular system [5,6,7]. Methamphetamine is an addictive drug that produces long-lasting and severe damage to the central nervous system [8]. The conditioned place preference (CPP) test is one of the most effective methods for the determination of animal reward. Research on drug dependence mainly focuses on rodents and other laboratory animals. A preliminary study found that rhynchophylline can eliminate the CPP effect in Evidence-Based Complementary and Alternative Medicine methamphetamine-dependent rats, and it is not addictive itself [9]
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