Dopaminergic signaling in prefrontal cortex contributes to the antidepressant effect of electroacupuncture: An iTRAQ‐based proteomics analysis in a rat model of CUMS

Abstract

Electroacupuncture (EA) is used as an adjunctive treatment for depression.This study was conducted to evaluate the efficacy and mechanisms of EA in the depressive rat model induced by chronic unpredictable mild stress (CUMS) in male adult Wistar rats. The underlying mechanisms were explored by using isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic analysis of the proteins in the prefrontal cortex (PFC), and observing the number of the PFC neurons stained with hematoxylin and eosin (H&E) and synaptic morphological changes under transmission electron microscopy (TEM). The results showed that EA plus paroxetine (EA + Par) for 1 week significantly relieved depression-like anhedonia symptoms and improved anxiety-like behavior, accompanied by the improvements in synaptic morphology and a significant increase of PFC neurons. Moreover, EA or paroxetine alone significantly alleviated anhedonia symptoms after 2 weeks of intervention. Additionally, iTRAQ analysis showed that dopaminergic signaling was significantly altered in CUMS rats after 1 week of EA treatment. As the critical enzyme of this pathway, aromatic-L-amino-acid decarboxylase (DDC) was significantly upregulated after the treatment with EA + Par for 1 week. These findings

Electroacupuncture alleviated depression‐like behaviors in ventromedial prefrontal cortex of chronic unpredictable mild stress‐induced rats: Increasing synaptic transmission and phosphorylating dopamine transporter

“…Based on our former research, 19 we further explored the vmPFC in CUMS rats in this study, now that the PFC is noteworthy for the realization of mood, learning, memory, execution, information integration, and other functions. The vmPFC in PFC integrates information from other brain regions such as the amygdala, striatum, ventral tegmental area (VTA), and temporal lobe, leading to the generation of negative emotions, self‐awareness, and self‐reflection.…”

“…The vmPFC receives neural projection from many other regions and is involved in one of the four dopaminergic pathways (the mesocortical pathway, connecting the ventral tegmentum to the PFC). Given our previous isobaric tags for relative and absolute quantitation (iTRAQ) finding of dopaminergic changes in the PFC, 19 the dopamine‐related mechanism in the vmPFC may be contributing to the alleviation of depressive symptoms.…”

“…26 Protein kinase A (PKA) is one of the major kinases phosphorylating DAT, acting at Ser7 of the N-terminal. 26 Our former iTRAQ exploration of the mechanism of EA on CUMS rat model discovered DAT-and PKA-related protein changes in PFC, 19 which provided the possibility between DAT phosphorylation via PKAinvolved signal pathway and depression.…”

Proteomics and its application in the research of acupuncture: An updated review

“…Therefore, these two acupoints are frequently used in combination for the treatment of depression [ 74 , 75 ]. Studies using samples from the prefrontal cortex have found that EA can alleviate symptoms of pleasure deficit, increase the number of PFC neurons and modulate dopaminergic signaling pathways to treat depression [ 76 ]. Analysis of the KEGG pathway revealed seven significantly enriched pathways in which the dopaminergic synapse, cocaine addiction, amphetamine addiction, and alcoholism pathways share the same four upregulated proteins.…”

“…KEGG pathway enrichment analysis suggested that oxidative phosphorylation was a major factor involved in the effects of EA therapy on DPN. [ 76 ] BCP EA ST36 BL60 30 min, 7/week, 1 weeks SD rats; the L4–L6 DRGs PEX100 protein microarray (antibody array); WB validation 176 DEPs 1. EA alleviated mechanical pain behavior and to some extent bone destruction in BCP rats.…”