Genomewide Analysis of Rat Periaqueductal Gray-Dorsal Horn Reveals Time-, Region- and Frequency-Specific mRNA Expression Changes in Response to Electroacupuncture Stimulation

Wang, Ke; Xiang, Xiao-Hui; Qiao, Nan; Qi, Jun-Yi; Lin, Li-Bo; Zhang, Rong; Shou, Xiao-Jing; Ping, Xingjie; Han, Ji-Sheng; Han, Jing–Dong Jackie; Zhao, Guoping; Cui, Cai-Lian

doi:10.1038/srep06713

Cited by 13 publications

(14 citation statements)

References 56 publications

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“…Effect of EA on physiological pain responses is a basis for understanding EA-induced analgesia. Ke et al [ 39 ] explored some probable EAA-related DEGs in rat PAGs and spinal cords under the physiological condition with cDNA microarray hybridization. However, this method with cDNA microarray hybridization and pooled RNAs only discovered limited information compared with high throughput screening and RNAs from individual samples.…”

Section: Discussionmentioning

confidence: 99%

Exploring the Mechanisms of Electroacupuncture-Induced Analgesia through RNA Sequencing of the Periaqueductal Gray

Zhu

Zhang

et al. 2017

IJMS

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Electroacupuncture (EA) can relieve various pains. However, its mechanism in terms of the transcriptome is still not well-known. To explore the full profile of EA-induced molecular modification in the central nerve system, three twins of goats were selected for a match-paired experiment: EA stimulation (60 Hz, 30 min) and none-EA (control). Goats in the EA group showed an increased (p < 0.05) nociceptive threshold compared with the control goats. Experimental goats were sacrificed at 4 h of the experiment, and the periaqueductal grays were harvested for RNA sequencing. As a result, 2651 differentially expressed genes (1803 up-regulated and 848 down-regulated genes) were found and enriched in 30 Kyoto Encyclopedia of Genes and Genomes pathways and 149 gene ontology terms. EA-regulated five neuropeptide genes (proenkephalin, proopiomelanocortin, preprodynorphin, diazepam-binding inhibitor and proprotein convertase 1 inhibitor) were validated with quantitative PCR. Furthermore, up-regulated glutamate receptors, glutamate transporters, γ-aminobutyric acid (GABA) receptors, GABA transporters, synaptotagmins or mitogen-activated protein kinase (MAPK) genes might contribute to EA-induced analgesia through regulating the glutamatergic synapse, GABAergic synapse, MAPKs, ribosome or ubiquitin-proteasome pathways. Our findings reveal a full profile of molecular modification in response to EA and provide a solid experimental framework for exploring the mechanisms underlying EA-induced analgesia.

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Section: Discussionmentioning

confidence: 99%

Exploring the Mechanisms of Electroacupuncture-Induced Analgesia through RNA Sequencing of the Periaqueductal Gray

Zhu

Zhang

et al. 2017

IJMS

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“…Wang et al [ 40 ] used EA to stimulate bilateral Zusanli and Kunlun acupoints in rabbits and found that better analgesia was induced by 2 Hz, followed by 30 Hz > 60 Hz > 100 Hz. Wang et al [ 41 ] reported that 100 Hz EA at bilateral Zusanli and Sanyinjiao acupoints induced more effective analgesia than 2 Hz in rats. Cao et al [ 42 ] reported that 15 Hz EA at bilateral Yanglingquan acupoints induced more effective analgesia than 100 Hz EA in rats.…”

Section: Discussionmentioning

confidence: 99%

Analgesic Neural Circuits Are Activated by Electroacupuncture at Two Sets of Acupoints

Qiu

et al. 2016

Evidence-Based Complementary and Alternative Medicine

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To investigate analgesic neural circuits activated by electroacupuncture (EA) at different sets of acupoints in the brain, goats were stimulated by EA at set of Baihui-Santai acupoints or set of Housanli acupoints for 30 min. The pain threshold was measured using the potassium iontophoresis method. The levels of c-Fos were determined with Streptavidin-Biotin Complex immunohistochemistry. The results showed pain threshold induced by EA at set of Baihui-Santai acupoints was 44.74% ± 4.56% higher than that by EA at set of Housanli acupoints (32.64% ± 5.04%). Compared with blank control, EA at two sets of acupoints increased c-Fos expression in the medial septal nucleus (MSN), the arcuate nucleus (ARC), the nucleus amygdala basalis (AB), the lateral habenula nucleus (HL), the ventrolateral periaqueductal grey (vlPAG), the locus coeruleus (LC), the nucleus raphe magnus (NRM), the pituitary gland, and spinal cord dorsal horn (SDH). Compared with EA at set of Housanli points, EA at set of Baihui-Santai points induced increased c-Fos expression in AB but decrease in MSN, the paraventricular nucleus of the hypothalamus, HL, and SDH. It suggests that ARC-PAG-NRM/LC-SDH and the hypothalamus-pituitary may be the common activated neural pathways taking part in EA-induced analgesia at the two sets of acupoints.

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“…Gene expression profiles of specific organs or tissues after EA stimulation at ST36 have also been analyzed. For example, gene expression profiles in periaqueductal gray-spinal dorsal horn region of rats after EA stimulation at ST36 and SP6 show that the modulation of neural-immune interaction in the central nervous system plays an important role during EA analgesia [ 22 ]. Gene expression profiling of rat arcuate nucleus region responsive to EA at ST36 and SP6 shows that the expression levels of genes are effectively regulated by low-frequency EA, compared with high-frequency EA.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive evaluation of gene expression signatures in response to electroacupuncture stimulation at Zusanli (ST36) acupoint by transcriptomic analysis

et al. 2017

BMC Complement Altern Med

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BackgroundElectroacupuncture (EA) has been applied to treat and prevent diseases for years. However, molecular events happened in both the acupunctured site and the internal organs after EA stimulation have not been clarified.MethodsHere we applied transcriptomic analysis to explore the gene expression signatures after EA stimulation. Mice were applied EA stimulation at ST36 for 15 min and nine tissues were collected three hours later for microarray analysis.ResultsWe found that EA affected the expression of genes not only in the acupunctured site but also in the internal organs. EA commonly affected biological networks involved in cytoskeleton and cell adhesion, and also regulated unique process networks in specific organs, such as γ-aminobutyric acid-ergic neurotransmission in brain and inflammation process in lung. In addition, EA affected the expression of genes related to various diseases, such as neurodegenerative diseases in brain and obstructive pulmonary diseases in lung.ConclusionsThis report applied, for the first time, a global comprehensive genome-wide approach to analyze the gene expression profiling of acupunctured site and internal organs after EA stimulation. The connection between gene expression signatures, biological processes, and diseases might provide a basis for prediction and explanation on the therapeutic potentials of acupuncture in organs.

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Genomewide Analysis of Rat Periaqueductal Gray-Dorsal Horn Reveals Time-, Region- and Frequency-Specific mRNA Expression Changes in Response to Electroacupuncture Stimulation

Cited by 13 publications

References 56 publications

Exploring the Mechanisms of Electroacupuncture-Induced Analgesia through RNA Sequencing of the Periaqueductal Gray

Exploring the Mechanisms of Electroacupuncture-Induced Analgesia through RNA Sequencing of the Periaqueductal Gray

Analgesic Neural Circuits Are Activated by Electroacupuncture at Two Sets of Acupoints

Comprehensive evaluation of gene expression signatures in response to electroacupuncture stimulation at Zusanli (ST36) acupoint by transcriptomic analysis

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