Table 5.
Summary of Animal Studies Determining the Mechanisms Underlying Acupuncture on PMI and PMD
| Author/Year | Animals | Disease Models | Methods of Modeling | Study Groups/No. of Participants | Interventions | Acupuncture Protocol | Acupoints | Outcome Measures | Results |
|---|---|---|---|---|---|---|---|---|---|
| Cao et al 2019152 | SD rats, 280–320g, 12 months | PMI | (i) OVX (ii) Electrical stimulation |
- EA/n= 12 - Model/n= 12 - Sham-surgery/n= 12 |
- EA/OVX + electrical stimulation + EA - Model/OVX + electrical stimulation - Sham-surgery/sham-OVX + electrical stimulation |
− 20 min/day for 14 days - Dense wave, 50Hz |
SP6 | (i) MER (REM, SWS) (ii) 5-HT, 5-HIAA, 5-HT1A in hippocampus |
(i) EA increased REM and SWS (ii) EA increased 5-HT and 5-HT1A levels; no significant change in 5-HIAA level |
| Cao et al 2020136 | Wistar rats, 230–270g, 5–7 months | PMI | (i) OVX (ii) Electrical stimulation |
- EA/n= 10 - Model/n= 10 - Sham-surgery/n= 10 |
- EA/OVX + electrical stimulation + EA - Model/OVX + electrical stimulation - Sham-surgery/sham-OVX + electrical stimulation |
− 15 min/day for 21 days - Dense wave, 50Hz |
EX-HN1, HT7 | (i) MER (TST, REM, SWS, LS) (ii) L-PGDS, PGD2, PGE2 in CSF (iii) GABA in VLPO |
(i) EA increased REM, SWS; no significant change in TST and LS (ii) EA increased L-PGDS and PGD2 levels; no significant change in PGE2 level (iii) EA increased GABA level |
| Jin et al 2010189 | SD rats, 230–270g, 3 months | PMI | (i) OVX (ii) Electrical stimulation |
- EA/n= 30 - Model/n= 30 - Sham-surgery/n= 30 |
- EA/OVX + electrical stimulation + EA - Model/OVX + electrical stimulation - Sham-surgery/sham-OVX + electrical stimulation |
− 30 min/day for 7 days - Continuous wave, 15Hz, 2mA |
BL23, SP6 | (i) SOL and TST (ii) Heat-resistant time (iii) Energy (iv) Times of locomotor activity |
(i) EA increased TST and reduced SOL (ii) EA increased heat-resistant time (iii) EA increased energy (iv) No significant change in times of locomotor activity (v) The earlier the intervention of EA in the perimenopausal period, the better the effect |
| Jin et al 2011190 | SD rats, 150–180g | PMI | (i) OVX (ii) Electrical stimulation |
- EA/n= 30 - Model/n= 30 - Sham-surgery/n= 30 |
- EA/OVX + electrical stimulation + EA - Model/OVX + electrical stimulation - Sham-surgery/sham-OVX + electrical stimulation |
− 30 min/day for 7 days - Continuous wave, 15Hz, 2mA |
BL23, SP6 | (i) SOL and TST (ii) Heat-resistant time (iii) Energy |
(i) EA increased TST and reduced SOL (ii) EA increased heat-resistant time (iii) EA increased energy (iv) The earlier the intervention of EA in the perimenopausal period, the better the effect |
| Xie 2013116 | SD rats, 216–245.8g, 6–8 weeks | PMI | OVX | - EA/n= 25 - Model/n= 25 - Sham-surgery/n= 25 - Sham-EA/n= 25 |
- EA/OVX + EA - Model/OVX - Sham-surgery/sham-OVX -Sham-EA/OVX + sham-EA |
− 15 min/day for 7 days - Continuous wave, 2Hz |
BL23, EX | (i) EEG/EMG recording systems for rats and mice (WASO, REM, NREM) (ii) Serum FSH, E2 (iii) Estrogen receptor in VLPO and TMN (iv) Weight |
(i) EA increased NREM, and reduced WASO and REM (ii) EA increased E2 and decreased FSH levels (iii) No significant change in estrogen receptor (iv) EA reduced weight |
| Yu 2012117 | SD rats, 230–270g, 6–8 weeks | PMI | OVX | - EA/n= 12 - Model/n= 12 - Sham-surgery/n= 12 - Sham-EA/n= 12 |
- EA/OVX + EA - Model/OVX - Sham-surgery/sham-OVX - Sham-EA/OVX + sham-EA |
− 15 min every other day for 7 days - Continuous wave, 2Hz |
EX | (i) EEG/EMG recording systems for rats and mice (WASO, REM, NREM) (ii) Serum FSH, E2, LH |
(i) EA increased NREM and reduced WASO; no significant change in REM; EA alleviated sleep fragmentation during the daytime (ii) EA increased E2 and reduced FSH levels; no significant change in LH level |
| Yang 2017121 | SD rats, 230–270g, 6–8 weeks | PMI | OVX | - EA/n= 40 - Model/n= 40 - Sham-surgery/n= 40 - Sham-EA/n= 40 |
- EA/OVX + EA - Model/OVX - Sham-surgery/sham-OVX - Sham-EA/OVX + sham-EA |
− 15 min/day for 7 days - Continuous wave, 15Hz |
BL23, EX | (i) EEG/EMG recording systems for rats and mice (WASO, REM, NREM) (ii) serum E2 and 5-HT (iii) Adrenocortical E2 (iv) Hypothalamic 5-HT, NE, ER-α mRNA, ER-β mRNA |
(i) EA increased NREM, and reduced WASO and REM; EA alleviated sleep fragmentation during the daytime (ii) EA increased E2 and 5-HT levels (iii) EA increased E2 level (iv) EA increased 5-HT, and decreased NE and ERβmRNA; no significant change in ERαmRNA |
| Jing et al 2020174 | SD rats, 190–210g, 56–62days | PMD | (i) OVX (ii) CUMS |
- EA/n= 10 - Control/n= 10 - Model/n= 10 - Sham-surgery/n= 10 - Clomipramine/n= 10 |
- EA/OVX + CUMS + EA - Control/no treatment - Model/OVX + CUMS - Sham-surgery/sham-OVX + CUMS - Clomipramine/OVX + CUMS + Clomipramine |
− 20 min/day for 28 days-isperse-dense wave, 4/20Hz, 18V | BL23, GV20, SP6 | (i) Behavioral tests (OFT, SPT) (ii) Serum E2, LH, GnRH (iii) GSK-3β mRNA, β-catenin mRNA in hippocampus (iv) β-Catenin protein, p-β-catenin protein in hippocampus |
(i) EA improved rats’ depression-like behavior in behavioral tests (ii) EA increased E2, and decreased LH and GnRH levels (iii) EA decreased GSK-3β mRNA and increased β-catenin mRNA expression (iii) EA increased β-catenin protein and decreased p-β-catenin protein expression |
| Guo et al 2019145 | KM mice, 18–22g | PMD | (i) OVX (ii) CUMS |
- EA/n= 10 - Control/n= 10 - Model/n= 10 - Clomipramine/n= 10 |
- EA/OVX + CUMS + EA - Control/no treatment - Model/OVX + CUMS - Clomipramine/OVX + CUMS + Clomipramine |
− 20 min/day for 28 days- disperse-dense wave, 2/10Hz, 18V |
BL23, GV20, SP6 | (i) Behavioral tests (FST, IAT, ADE, TSE) (ii) Serum E2, FSH, LH (iii) 5-HT, NE, DA in hippocampus |
(i) EA improved mice’ depression-like behavior in behavioral tests (ii) EA increased E2 and decreased LH and FSH levels (ii) EA increased 5-HT, NE and DA levels |
| Seo et al 2018170 | SD rats, 250–300g | PMD | OVX | - EA/n= NR - Model/n= NR - Sham-surgery/n= NR -Sham-EA/n= NR |
- EA/OVX + EA - Model/OVX - Sham-surgery/sham-OVX - Sham-EA/OVX + sham-EA |
60 seconds/day for 4 days | SP6 | (i) Behavioral tests (FST, OFT, EPM) (ii) E2 and estrogen receptor expression in plasma and hippocampus (iii) BDNF and p-TrkB receptor in hippocampus (iv) NPY in hippocampus |
(i) EA improved rats’ depression-like behavior in behavioral tests (ii) no significant change in E2 level or estrogen receptor expression (iii) EA increased BDNF and p-TrkB receptor levels (iv) EA increased NPY levels |
| Deng et al 2017185 | SD rats, 190–210g, 56–62days | PMD | (i) OVX (ii) CUMS |
- EA/n= 12 - Control/n= 12 - Model/n= 12 - Clomipramine/n= 12 |
- EA/OVX + CUMS + EA - Control/no treatment - Model/OVX + CUMS - Clomipramine/OVX + CUMS + Clomipramine |
− 20 min/day for 28 days- disperse-dense wave, 4/20Hz, 18V |
BL23, GV20, SP6 | (i) Behavioral tests (FST, OFT) (ii) MAP-2, Notch1, Jagged1, Hes1 in hippocampus (iii) MAP-2 mRNA, Notch1 mRNA, Jagged1 mRNA, Hes1 mRNA in hippocampus |
(i) EA improved rats’ depression-like behavior in behavioral tests (ii) EA increased MAP-2 protein and Notch1 protein levels, and decreased Jagged1 protein and Hes1 protein levels (ii) EA increased MAP-2 mRNA and Notch1 mRNA expression, and decreased Jagged1 mRNA and Hes1 mRNA expression |
| Deng 2017177 | SD rats, 190–210g, 56–62days | PMD | (i) OVX (ii) CUMS |
- EA/n= 10 - Control/n= 10 - Model/n= 10 - Sham-surgery/n= 10 - Clomipramine/n= 10 |
- EA/OVX + CUMS + EA - Control/no treatment - Model/OVX + CUMS - Sham-surgery/sham-OVX + CUMS - Clomipramine/OVX + CUMS + Clomipramine |
− 20 min/day for 28 days- disperse-dense wave, 4/20Hz, 18V |
BL23, GV20, SP6 | (i) Behavioral tests (FST, OFT, SPT) (ii) GSK-3β, β-catenin in hippocampus (iii) β-catenin protein, p-β-catenin protein in hippocampus (iv) GSK-3β mRNA, β-catenin mRNA in hippocampus |
(i) EA improved rats’ depression-like behavior in behavioral tests (ii) EA decreased GSK-3β and increased β-catenin contents (iii) EA increased β-catenin protein expression; no significant change in p-β-catenin protein expression (iv) EA decreased GSK-3β mRNA and increased β-catenin mRNA expression |
| Huangfu 2018129 | SD rats, 190–210g, 56–62days | PMD | (i) OVX (ii) CUMS |
- EA/n= 10 - Control/n= 10 - Model/n= 10 - Clomipramine/n= 10 |
- EA/OVX + CUMS + EA - Control/no treatment - Model/OVX + CUMS - Clomipramine/OVX + CUMS + Clomipramine |
− 20 min/day for 28 days- disperse-dense wave, 4/20Hz, 18V |
BL23, GV20, SP6 | (i) Behavioral tests (FST, OFT, SPT, TSE) (ii) Glucocorticoid receptor, mineralocorticoid receptor in hippocampus |
(ii) EA improved rats’ depression-like behavior in behavioral tests (ii) EA increased glucocorticoid receptor and mineralocorticoid receptor levels |
| Jiang 2017124 | SD rats, 190–210g, 56–62days | PMD | (i) OVX (ii) CUMS |
- EA/n= 12 - Control/n= 12 - Model/n= 12 - Sham-surgery/n= 12 - Clomipramine/n= 12 |
- EA/OVX + CUMS + EA - Control/no treatment - Model/OVX + CUMS - Sham-surgery/sham-OVX + CUMS - Clomipramine/OVX + CUMS + Clomipramine |
− 20 min/day for 28 days- disperse-dense wave, 4/20Hz, 18V |
BL23, GV20, SP6 | (i) Behavioral tests (FST, SPT, TSE) (ii) Serum E2, FSH, LH, GnRH, CRH, ACTH, CORT, β-EP |
(i) EA improved rats’ depression-like behavior in behavioral tests (ii) EA increased E2 andβ-EP, and decreased FSH, LH, GnRH, CORT, ACTH and CRH levels |
| Jiang et al 2017127 | SD rats, 190–210g, 8–9 weeks | PMD | (i) OVX (ii) CUMS |
- EA/n= 12 - Control/n= 12 - Model/n= 12 - Sham-surgery/n= 12 - Clomipramine/n= 12 |
- EA/OVX + CUMS + EA - Control/no treatment - Model/OVX + CUMS - Sham-surgery/sham-OVX + CUMS - Clomipramine/OVX + CUMS + Clomipramine |
− 20 min/day for 28 days- disperse-dense wave, 4/20Hz, 18V |
BL23, GV20, SP6 | (i) Behavioral test (SPT) (ii) Serum E2, LH, GnRH, β-EP |
(i) EA improved rats’ depression-like behavior in behavioral test (ii) EA increased E2 andβ-EP, and decreased LH and GnRH levels |
| Jing et al 2018178 | SD rats, 180–220g, 17 weeks | PMD | (i) OVX (ii) CUMS |
- EA/n= 12 - Control/n= 12 - Model/n= 12 - Clomipramine/n= 12 |
- EA/OVX + CUMS + EA - Control/no treatment - Model/OVX + CUMS - Clomipramine/OVX + CUMS + Clomipramine |
− 20 min/day for 28 days- disperse-dense wave, 2/10Hz, 18V |
BL23, GV20, SP6 | (i) Behavioral test (TSE) (ii) E2, NE in hippocampus (iii) DKK1, LRP-5, LRP-6 in hippocampus |
(i) EA improved rats’ depression-like behavior in behavioral test (ii) EA increased E2 and NE levels (iii) EA decreased DKK1, and decreased LRP-5 and LRP-6 expression |
| Zhou et al 2015146 | SD rats, 220–260g | PMD | (i) OVX (ii) CUMS |
- MA/n= 9 - Model-1/n= 9 - Model-2/n= 8 - Sham-surgery/n= 6 - Nilestriol + Fluoxetine/n= 9 |
- MA/OVX + CUMS + MA - Model-1/OVX + CUMS - Model-2/OVX - Sham-surgery/sham-OVX - Nilestriol + Fluoxetine/OVX + CUMS + Nilestriol + Fluoxetine |
20 min/day for 21 days | BL23, GV20, SP6 | (i) Behavioral test (OFT) (ii) 5-HT, NE, DA in hypothalamus |
(i) MA improved rats’ depression-like behavior in behavioral test (ii) MA increased 5-HT level; no significant changes in NE and DA levels |
| Shi et al 2012147 | SD rats, 300–350g, 4 months | PMD | (i) OVX (ii) CUMS |
- MA/n= 10 - Model/n= 5 - Sham-surgery/n= 5 - Estradiol benzoate/n= 10 |
- MA/OVX + CUMS + MA - Model/OVX + CUMS - Sham-surgery/sham-OVX + CUMS - Estradiol benzoate/OVX + CUMS + Estradiol benzoate |
30 min/session, once session every 2 days for total 30 sessions | CV4, CV6, LI4, LR3, PC6, SP6, ST36 | (i) Serum E2 (ii) 5-HT in hypothalamus |
(i) EA increased E2 level (ii) EA increased 5-HT level |
| Sun 2009118 | (i) SD rats, 250–300g, 11–15 months (n= 45) (ii) Young SD rats, 150–200g, 4 months (n= 10) |
PMD | CUMS | - EA/n= 15 - Model/n= 15 - Clomipramine/n= 15 - Young/n= 10 |
- EA/CUMS + EA - Model/CUMS - Clomipramine/CUMS + Clomipramine - Young/CUMS |
− 20 min/day for 7 days- disperse-dense wave, 4/20Hz, 2V |
BL18, BL23, GV20, SP6 | (i) Behavioral tests (OFT) (ii) Serum E2, NE |
(i) EA improved rats’ depression-like behavior in behavioral test (ii) EA increased E2 and NE levels |
| Wang et al 2016171 | SD rats, 220–260g, 17weeks | PMD | (i) OVX (ii) CUMS |
- EA/n= 10 - Control/n= 10 - Model/n= 10 - Clomipramine/n= 10 |
- EA/OVX + CUMS + EA - Control/no treatment - Model/OVX + CUMS - Clomipramine/OVX + CUMS + Clomipramine |
− 20 min/day for 28 days- disperse-dense wave, 2/10Hz |
BL23, GV20, SP6 | (i) Behavioral test (OFT) (ii) CREB, BDNF in hippocampus |
(i) EA improved rats’ depression-like behavior in behavioral test (ii) EA increased BDNF and CREB levels |
| Wu 2012148 | (i) SD rats, 260–471g, 11–13 months (n= 73) (ii) Young SD rats, 140–191g, 4 months (n= 20) |
PMD | CUMS | - EA/n= 18 - Model/n= 19 - Clomipramine/n= 18 - Herbal medicine/n= 18 - Young/n= 20 |
- EA/CUMS + EA - Model/CUMS - Clomipramine/CUMS + Clomipramine - Herbal medicine/ CUMS + XiaoYao-Pill - Young/CUMS |
− 20 min/day for 10 days- disperse-dense wave, 2/15Hz, 2V |
BL18, BL23, GV20, SP6, ST36 | (i) Behavioral test (OFT) (ii) Serum E2 (iii) 5-HT2A mRNA, p-ERK 1/2 in hippocampus |
(i) EA improved rats’ depression-like behavior in behavioral test (ii) EA increased E2 level (ii) EA decreased 5-HT2A mRNA expression; EA increased p-ERK 1/2 expression |
| Zhang 2009128 | (i) SD rats, 250–300g, 11–15 months (n= 45) (ii) Young SD rats, 150–200g, 4 months (n= 10) |
PMD | CUMS | - EA/n= 15 - Model/n= 15 - Clomipramine/n= 15 - Young/n= 10 |
- EA/CUMS + EA - Model/CUMS - Clomipramine/CUMS + Clomipramine - Young/CUMS |
− 20 min/day for 7 days- continuous wave, 20Hz, 2V |
BL18, BL23, GV20, SP6 | (i) Behavioral test (OFT) (ii) Serum E2 (iii) β-EP in hippocampus |
(i) EA improved rats’ depression-like behavior in behavioral test (ii) EA increased E2 level (ii) EA increased β-EP level |
| Zhao et al 2011149 | (i) SD rats, 260–471g, 11–13 months (n= 66) (ii) Young SD rats, 140–191g, 4 months (n= 20) |
PMD | CUMS | - EA/n= 15 - Model/n= 18 - Clomipramine/n= 17 - Herbal medicine/n= 16 - Young/n= 20 |
- EA/CUMS + EA - Model/CUMS - Clomipramine/CUMS + Clomipramine - Herbal medicine/ CUMS + XiaoYao-Pill - Young/CUMS |
− 20 min/day for 28 days | BL18, BL23, GV20, SP6, ST36 | (i) Behavioral test (OFT) (ii) Serum 5-HT, HDL |
(i) EA improved rats’ depression-like behavior in behavioral test (ii) EA increased 5-HT and HDL levels |
| Song et al 2021119 | KM mice, 18–22g, 5–6 weeks | PMD | (i) OVX (ii) Ice-water swimming stimulation (I-WSS) |
- EA/n= 10 - Control/n= 10 - Model/n= 10 |
- MA/OVX + I-WSS + MA - Control/I-WSS - Model/OVX + I-WSS |
− 30 min/day, 6 days/week for 4 weeks | CV4, KI3, KI15, SP6, SP10, ST36 | Serum E2 | EA increased E2 level |
Abbreviations: NR, no report; PMI, perimenopausal insomnia; PMD, perimenopausal depression; MA, manual acupuncture; EA, electroacupuncture; OVX, ovariectomy; CUMS, chronic unpredictable mild stress; MER, multichannel electrophysiological recordings; SOL, sleep onset latency; TST, total sleep time; WASO, wake after sleep onset; REM, rapid eye movement; NREM, non-rapid eye movement; LS, light sleep; SWS, slow wave sleep; FSH, follicle-stimulating hormone; LH, luteinizing hormone; E2, estradiol; CSF, cerebrospinal fluid; VLPO, ventrolateral preoptic; TMN, tuberomammillary nucleus; PGD2, prostaglandin D2; PGE2, prostaglandin E2; L-PGDS, lipocalin-type prostaglandin D synthase; GABA, gamma-amino butyric acid; 5-HT, 5-hydroxytryptamine; 5-HIAA, 5-hydroxyindole acetic acid; NE, norepinephrine; DA, dopamine; ER-α, Estrogen receptor-α; ER-β, Estrogen receptor-β; GnRH, gonadotropin-releasing hormone; GSK-3β, glycogen synthase kinase-3β; p-β-catenin, phosphorylated β-catenin; BDNF, brain-derived neurotrophic factor; NPY, neuropeptide Y; MAP-2, microtubule- associated protein-2; CRH, corticotropin releasing hormone; ACTH, adrenocorticotropic hormone; CORT, cortisol; β-EP, beta-endorphin; DKK1, Dickkopf1; LRP-5, low density lipoprotein receptor related protein 5; LRP-6, low density lipoprotein receptor related protein 6; CREB, cyclic-AMP response binding protein; p-ERK 1/2, phosphorylated-extracellular regulated kinase 1/2; HDL, high-density lipoprotein; CUMS, chronic unpredictable mild stress; SPT, sucrose preference test; OFT, open field test; FST, forced swimming test; IAT, independent activity test; ADE, avoiding dark experiment; TSE, tail suspension experiment; EPM, elevated plus maze; BL18, Ganshu; BL23, Shenshu; CV4, Guanyuan; CV6, Qihai; EX, Anmian; EX-HN1, Sishencong; GV20, Baihui; HT7, Shenmen; KI3, Taixi; KI15, Zhongzhu; LI4, Hegu; LR3, Taichong; PC6, Neiguan; SP6, Sanyinjiao; SP10, Xuehai; ST36, Zusanli.