Table 3 Proposed mechanisms of acupuncture in behavior changes in depression models of studies included.

From: Acupuncture for behavioral changes of experimental depressive disorder: a systematic review and meta-analysis

Research

Proposed mechanisms

Bao 201411

Increased 5-HT in serum.

Bao 2014#12

Relieved impairment of hippocampal neurons.

Chen 201113

Increased expression of Bcl-2 in hippocampus.

Decreased expression of Bax in hippocampus.

Cheng 201514

Regulated the expression of IL-6R in frontal cortex and hippocampus.

Dai 201015

Down-regulated level of phospho-JNK in hippocampus.

Reduced hippocampal apoptotic rate.

Deng 201316

Decreased expressions of IL-1β, IL-6 in hippocampus and serum.

Duan 200818

Increased p-CREB in hippocampus.

Duan 201619

Increased 5-HT, Glu, GABA in hippocampus.

Increased levels of TrkB, BDNF, p-CREB,PKA and decreased CaMKII in the hippocampus.

Up-regulated expression levels of PKA mRNA and TrkB mRNA and down-regulated expression levels of CaMKII mRNA in the hippocampus.

Duan 2016#20

Increased 5-HT in hippocampus.

Increased 5-HIAA level.

Up-regulated levels of TPH and 5-HT1A.

Up-regulated expression levels of TPH mRNA and 5-HT1A mRNA.

Fan 201321

Decreased IL-2,IL-6 and NO in serum.

Fan 201622

Regulated levels of 5-HT, NE, BDNF and expression of Bax/Bcl-2.

Fan 2016#23

Down-regulated expressions of SNAP25, VAMP1, VAMP2, VAMP7 and syntaxin1.

Fan 2016*24

Down-regulated expressions of SNAP25, VAMP1, VAMP2, VAMP7 and syntaxin1.

Fu 200825

Up-regulated expressions of CREB, BDNF in hippocampus.

Guo 201626

Decreased level of ROS in hippocampus.

Decreased protein expression levels of cytochrome C,caspase-3, and AIF in hippocampus

Hu 201327

Decreased IL-1β,IL-6,TNF-α in serum, hippocampus and frontal cortex.

Hu 201428

Down-regulated expressions of RAGE, Activin A, CNTF Rα, EGFR, E-Selectin, and Resistin in hippocampus.

Decreased IL-1β, IL-10 in hippocampus.

Huang 200529

Decreased CORT,ACTH in serum.

Ji 201330

Increased the GFAP and astrocyte in hippocampus.

Jia 200531

Decreased IL-1, CRF in hypothalamus.

Decreased CRF in hypophysis.

Decreased ACTH, CORT in adrenal gland.

Down-regulated expressions of CRF1mRNA, POMC mRNA in hypophysis.

Up-regulated expressions of GRmRNA in hippocampus, hypothalamus, hypophysis and MRmRNA, 5-HT1AmRNA in hippocampus.

Jiang 200732

Incresed cAMP in hippocampus.

Up-regulated expressions of CREB,BDNF in hippocampus.

Jiang 201333

Repaired astrocytes in CA1, DG area in hippocampus.

Increased GFAP, GFAPmRNA in hippocampus.

Jin 201535

Down-regulated expression of NF-kB, COX-2, and COX-2 mRN in hippocampus and decreased PGE2 in hippocampus.

Jing 201636

Down-regulated the expression of PDE4A and PDE4D mRNA in hippocampus.

Li 200737

Increased cAMP in hippocampus.

Li 200838

Increased bcl-2 in hippocampus.

Reduced hippocampal apoptotic rate.

Li 201139

Regulated the gene expression of Dnmt3L and MBP in hippocampus.

Li 2011&40

Increased β-EP in serum and µ receptors level in hypothalamus.

Li 201441

Increased 5-HT and 5-HTT in hippocampus.

Lin 200842

Increased BDNF in the hippocampal. Dncreased TGF-β1 in serum.

Liu 200844

Regulated GFAP,BDNF,GDNF in hippocampus.

Liu 200945

Increased 5-HT,DA,NE in hippocampus.

Liu 201246

Incresed AC transformation ratio,cAMP level, and PKA activity.

Lu 200847

Reduced CORT in serum.

Increased expressions of PKA and PKC in hippocampus.

Lu 201348

Regulated levels of ERK1/2,p-ERK1/2, CREB, p-CREB in the hippocampus.

Lu 201649

Reduced levels of NO, PGE2, iNOS and COX-2 in the hippocampus and prefrontal cortex.

Inhibited the activation of NF-kB in the hippocampus and prefrontal cortex.

Lu 2016#50

Increased the mRNA and protein expression of IL-1β, IL-6, and TNF-α in the hippocampus and prefrontal cortex and cytokine concentrations in serum.

Luo 201651

Regulated GS,EAAT1,EAAT2 of astrocyte cell in prefrontal cortex.

Ma 201652

Upregulated expression of TRH and TRH mRNA in the hypothalamus.

Mo 201453

Upregulated expression of TRH and TRH mRNA in the hypothalamus.

Pan 201654

Regulated Glu, GABA in hippocampal

Increased DA,5-HT in serum.

Regulated expressions of GAD65, EATT3,GAT1, NR2B in hippocampal.

Qin 201055

Increased NT in hypothalamus and ileum.

Shao 201656

Downregulated expressions of NF-kB, NO, iNOS.

Shi 200757

Reduced levels of CORT,ACTH,CRH.

Shi 201558

Increased 5-HT in hippocampal and BDNF in serum levels,and decreased CORT in adrenal.

Song 201459

Increased the production of MT.

Regulated ET, NO, ET-1 in serum.

Regulated leves of renin Ang II (Angiotensin II), AT1R (Angiotensin II Type 1 Receptor), ACE (Angiotensin converting enzyme).

Regulated MOD, SOD in serum.

Song 201560

Regulated BDNF, bcl-2, CREB,and EPK signaling pathway.

Song 201661

Reduced CORT,ACTH,CRH in serum.

Song 2014#62

Down-regulated expression of AngII, AT1R and ACE I in the arterial tissue.

Sun 201364

Promoted repair of astrocytes.

Sun 201465

Down-regulated expression of p-JNK, c-jun, Caspase-3.

Sun 201666

Decreased CORT, ACTH in serum.

Tang 201367

Increased 5-HT,DA,NE in hippocampus.

Tang 201468

Increased 5-HT,DA,NE in hippocampus and loubus fromatis.

Teng 201369

Increased GAS and reduced NPY,CGRP in colonic mucosa,increased GAS,NPY,CGRP in hypothalamus.

Increased β-EP in hypothalamus and reduced β-EP in colonic mucosa.

Wang 200971

Incresed expression of 5-HT2A receptor mRNA in hippocampus.

Reduced expression of 5-HT1A receptor mRNA in hippocampus.

Wang 201072

Increased BDNF in hippocampus.

Wang 201373

Regulated β-EP in serum and brain tissue.

Wang 201675

Promoted repair of hippocampus CA3 region.

Wu 200776

Repaired the lesion of multiple organs.

Promoted 5-HT synthesis.

Xiao 201477

Improved expression of GS mRNA, EAAT1 mRNA,EAAT2 mRNA.

Xiao 2014&78

Improved the injury of hippocampal astrocytes.

Xu 201679

Up-regulated level of TGF-3β in hippocampal and down-regulated expression of bFGF.

Xu 2016#80

Regulated levels of ERK1/2, p-ERK1/2, CREB, p-CREB and BDNF in the hippocampus.

Yang 2013#82

Regulated levels of TrkB and BDNF.

Yu 201284

Increased 5-HT,DA,NE in brain.

Yu 201685

Regulated levels of PKA,CREB in prefrontal cortex and IL-6,TNF-α in serum.

Zhang 200888

Reduced CORT and CRF.

Improved expression of GR,NMDA,NR2B, PKA, CREB, Nestin in hippocampus.

Zhang 201689

Regulated levels of ERK1/2,p-ERK1/2, CREB, p-CREB and BDNF in the hippocampus.

Zhang# 201690

Regulated Glu,GABA in hippocampus.

Down-regulated expressions of NMDA-receptor subunits NRl and NR2A in hippocampus.

Zhang 2016&91

Increased GFAP,GS,Glu-C4,Gln-C4,GABA-C2 in prefrontal cortex and hippocampus.

Zhang 2016*92

Regulated BDNF, acH3K9, HDAC2 and PKA signaling pathway.

Zhao 200593

Reduced CORT,ACTH in serum.

Increased 5-HT, NE in brain.

Zheng 201394

Down-regulated expression of CRF in hypothalamus.

  1. Notes: β-EP, β-endorphin; p-CREB, phosp-horylated cAMP response element binding protein; 5-HT, 5-hydroxytryptamine; 5-HT1A: 5-hydroxyindoleacetic acid; 5-HTT, 5-hydroxytryptamine transporter; ACEI, Angiotensin converting enzyme I; acH3K9, acetylation of histone 3 lysine 9; ACTH, adrenocorticotropic hormone; AIF, apotposis inducing factor; AngII, angiotensin II; AT1R, angiotensin II Type 1 Receptor; Bax, Bcl-2 Assaciated X protein; Bcl-2, B-cell lymphoma 2; BDNF, brain derived neurotrophic factor; bFGF, basic fibroblast growth factor; CaMKII, calcium-calmodulin-dependent protein kinase II; cAMP, adenosine 3’, 5’-cyclic monophos-phate; CGRP, calcitonin generelated peptide; CNTF Rα, ciliary neurotrophic factor receptor α; CORT, corticoserone; COX-2, cyclo-oxygenase-2; CRF, corticotropin releasing factor; CRH, corticotropin releasing hormone; DA, Dopi Amine; Dnmt, DNA methytransferase; EAAT1, excitatory amino acid transporter 1; EAAT2, excitatory amino acid transporter 2; EGFR, epithelial growth factor receptor; ERK, extracellular signal-regulated kinase; GABA, γ-aminobutyric acid; GAS, Gastrin; GDNF, glial cell line-derived neurotrophic factor. GFAP, glial fibrillary acidic protein; Gln, glutamine; Glu, glutamate; GR, glucocorticoid receptor; GS, glutamine synthetase; HDAC2, histone deacetylase 2; HPA, hypothalamus-pituitary-adrenal; IL-1β, Interleukin-1β; IL-6, interleukin-6; IL-6r, Interleukin-6r; IL-10, Interleukin-10; iNOS, inducible Nitric Oxide Synchase; JNK, c-Jun N-terminal kinasesignal; MBP: myelin basic protein; MLT, motilin; MOD, Malondialdehyde; MT, melatonin; NE, norepinephrine; Nestin, neuroepithelial stem protein; NF-kB, nuclear factor kappa B; NMDA, N-methy-D-aspartate; NO, nitric oxide; NPY, neuropeptide-y; NR2B, NMDA receptor subunits 2B; NT, neurotensin; PDE4, phosphodiesterase 4; PGE2, prostaglandin E2; PKA, protein kinase A; PKC, protein kinase C; RAGE, receptor for advanced glycation end-products; RAS, renin-angiotensin system; ROS, reactive oxygen species; SNAP, synaptic soluble Nethylmaleimide-sensitive factor attachment receptor; SOD, Superoxide dismutase; SS, somatostatin; TGF-3β, transforming growth factor beta 3; TNF-α, tumor necrosis factor-α; TPH, tryptophan hydroxylase; TRH,Thyrotropin releasing hormone; TrkB, tropomyosin receptor kinase B; VAMP, vesicle-associated membrane protein.
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