Effect of Electroacupuncture on Reuptake of Serotonin via miRNA-16 Expression in a Rat Model of Depression

Abstract

The current study aimed to investigate the effects and mechanisms of electroacupuncture (EA) treatment applied to Bai hui (GV20) and Yin tang (GV29) acupoints (1 mA, 2 Hz, continuous wave, 20 minutes) for 28 days in a rat model of chronic unpredictable mild stress (CUMS) on reuptake of serotonin (5-hydroxytryptamine (5-HT)) and miRNA-16 levels in the hippocampus and serum. Rats were housed in individual cages, and CUMS was used to establish a rat model of depression. After EA treatment for 4 weeks, behavioral changes and indices including 5-HT transporter (SERT), 5-HT, and miRNA-16 levels in the hippocampus and serum were examined. The EA treatment significantly improved base levels of sucrose preference and exploratory behavior and significantly decreased SERT protein and mRNA expression in the hippocampus of depressed rats. Significantly increased 5-HT levels were observed, and miRNA-16 levels were significantly decreased in the hippocampus and serum of depressed rats. In conclusion, the antidepressant effects of EA treatment may be affected via inhibition of 5-HT reuptake, upregulation of 5-HT levels, and inhibition of miRNA-16 expression in the hippocampus and serum.

EA Ameliorated Depressive Behaviors in CUMS Rats and Was Related to Its Suppressing Autophagy in the Hippocampus

“…One of the major brain areas where EA ameliorates depressive behaviors of animals is the hippocampus, in which several mechanisms have been confirmed, such as synaptic plasticity, neuroinflammation, and neurotransmitter upregulation [ 48 – 50 ]. However, whether and how autophagy participates in the regulation of EA on depression are unclear yet.…”

Early Life Stress and the Onset of Obesity: Proof of MicroRNAs’ Involvement Through Modulation of Serotonin and Dopamine Systems’ Homeostasis

“…As far as we know, miR-16 is able to bind the SERT messenger ( Table 2 ) and silence its expression in humans and animals ( Baudry et al, 2010 ; Moya et al, 2013 ; Song et al, 2015 ; Shao et al, 2018 ). The relationship between miR-16 and SERT is even modulated by pharmacological antidepressant treatment and also alternative treatments as the electroacupuncture; besides different responses according to the affected brain area, these treatments improve the level of depressive behaviors, suggesting a highly specific regulation ( Baudry et al, 2010 ; Zhao et al, 2019 ). SERT appears to be a key piece of regulation, as different miRNAs can modify its expression, as the mmu-miR-135 ( Issler et al, 2014 ), rno-miR-18a-5p, rno-miR-34a-5p, rno-miR-135a-5p, rno-miR-195-5p, rno-miR-320-3p, rno-miR-674-3p, and rno-miR-872-5p ( Zurawek et al, 2017 ).…”

Applications of Acupuncture Therapy in Modulating the Plasticity of Neurodegenerative Disease and Depression: Do MicroRNA and Neurotrophin BDNF Shed Light on the Underlying Mechanism?

“…The 3′-UTR of BDNF was also targeted by miR-16, which mediates the action of the antidepressant fluoxetine by acting as a micromanager of hippocampal neurogenesis [ 122 ]. Most interestingly, numerous studies have shown that EA can not only inhibit the expression of miR-16 in the hippocampus [ 132 ] but also increase the levels of BDNF in the brains of depression model rats [ 126 – 130 ]. Therefore, acupuncture promoted synaptic plasticity via BDNF protein expression and regulated a few miRNAs that were found to target BDNF, which seem to play important roles in the development of depression.…”

“…The CUMS rat model was used, and EA was administered at acupoints GV20 and GV29. After the administration of EA, depression-like behaviours were improved, and high expression of miR-16 in the hippocampus was inhibited as well [ 132 ]. Regrettably, this study did not directly explore the relationship between EA regulation of BDNF and neural plasticity.…”