Efficacy of electroacupuncture stimulating Shenmen (HT7), Baihui (GV20), Sanyinjiao (SP6) on spatial learning and memory deficits in rats with insomnia induced by para-chlorophenylalanine: a single acupoint vs combined acupoints

doi:10.19852/j.cnki.jtcm.20230308.001

Abstract

Abstract:

OBJECTIVE: To investiage the effect of electroacupuncture (EA) at a single acupoint of Shenmen (HT7), Baihui (GV20), Sanyinjiao (SP6) and at combined acupoints of Shenmen (HT7) and Baihui (GV20) and Sanyinjiao (SP6) on the PKA/CREB and BDNF/TrkB signaling, as well as neuroapoptosis and neurogenesis in hippocampus and elucidate the underlying mechanism of single and combined acupoints on ameliorating spatial learning and memory deficits in a rat model of primary insomnia.

METHODS: Primary insomnia was modeled by intraperitoneal injection of para-chlorophenylalanine (PCPA) once daily for 2 d. EA was applied at Shenmen (HT7), Baihui (GV20), Sanyinjiao (SP6), or Shenmen (HT7) + Baihui (GV20) + Sanyinjiao (SP6) (combined) for 30 min daily for 4 d. Spatial learning and memory function was evaluated by the Morris water maze (MWM) test. Protein expressions of hippocampal cAMP-dependent protein kinase (PKA)-Cβ, phosphorylated cAMP-responsive element-binding protein (p-CREB), brain-derived neurotrophic factor (BDNF), and tyrosine kinase receptor B (TrkB) were evaluated by Western blotting. Neuronal apoptosis in the hippocampus was detected with the transferase-mediated dUTP-X nick end labeling assay. Endogenous neurogenesis was examined with bromodeoxyuridine staining. The MWM test and hippocampal p-CREB, BDNF, and TrkB protein levels in the combined acupoints group were evaluated after the administration of a PKA-selective inhibitor (H89).

RESULTS: Spatial learning and memory were significantly impaired in rats with insomnia. The spatial learning deficits were ameliorated in the Shenmen (HT7), Baihui (GV20), Sanyinjiao (SP6), and combined groups; this improvement was significantly greater in the combined group than the single acupoint groups. The spatial memory impairment was improved in the combined, Baihui (GV20), and Shenmen (HT7) groups, but not the Sanyinjiao (SP6) group. The expressions of PKA-Cβ, p-CREB, BDNF, and TrkB were decreased in rats with insomnia. All these proteins were significantly upregulated in the combined group. PKA/p-CREB protein levels were elevated in the Baihui (GV20) and Shenmen (HT7) groups, whereas BDNF/TrkB expression was upregulated in the Sanyinjiao (SP6) group. The staining results showed significant attenuation of hippocampal cell apoptosis and increased numbers of proliferating cells in the combined group, whereas the single acupoint groups only showed decreased numbers of apoptotic cells. In the combined group, the PKA inhibitor reversed the improvement of spatial memory and upregulation of p-CREB expression caused by EA, but did not affect its activation of BDNF/TrkB signaling.

CONCLUSIONS: EA at the single acupoints Baihui (GV20), Shenmen (HT7), or Sanyinjiao (SP6) had an ameliorating effect on the spatial learning and memory deficits induced by insomnia. EA at combined acupoints exerted a synergistic effect on the improvements in spatial learning and memory impairment in rats with insomnia by upregulating the hippocampal PKA/CREB and BDNF/TrkB signaling, facilitating neurogenesis, and inhibiting neuronal apoptosis. These findings indicate that EA at combined acupoints [(Baihui (GV20), Shenmen (HT7), and Sanyinjiao (SP6)] achieves a more pronounced regulation of hippocampal neuroplasticity than EA at single acupoints, which may partly explain the underlying mechanisms by which EA at combined acupoints exerts a better ameliorative effect on the cognitive dysfunction caused by insomnia.

Key words: sleep initiation and maintenance disorders, learning, memory, hippocampus, neuronal plasticity, acupoints combination

QIAO Lina, SHI Yinan, TAN Lianhong, JIANG Yanshu, YANG Yongsheng. Efficacy of electroacupuncture stimulating Shenmen (HT7), Baihui (GV20), Sanyinjiao (SP6) on spatial learning and memory deficits in rats with insomnia induced by para-chlorophenylalanine: a single acupoint vs combined acupoints[J]. Journal of Traditional Chinese Medicine, 2023, 43(4): 704-714.

Figures/Tables 4

Figure 1 Evaluation of the effects of EA on spatial learning and memory dysfunction of rats with insomnia using the MWM test A: escape latency time of the six groups in the orientation navigation trial on days 1-4. B: platform crossing times of the six groups in the space exploration trial on day 4. Normal: control group, Model: injected with PCPA, Shenmen (HT7): model mice with EA at Shenmen (HT7), Baihui (GV20): model mice with EA at Baihui (GV20), Sanyinjiao (SP6): model mice with EA at Sanyinjiao (SP6), Combined: model mice with EA at Shenmen (HT7), Baihui (GV20) and Sanyinjiao (SP6). PCPA: para-chlorophenylalanine; EA: electroacupuncture; MWM: Morris water maze. aP < 0.05, compared with the normal group; bP < 0.05, compared with the model group; cP < 0.05, compared with the Shenmen (HT7) group; dP < 0.05, compared with the Baihui (GV20) group; eP < 0.05, compared with the Sanyinjiao (SP6) group (n = 11). Data are presented as mean ± standard deviation. Statistics by one-way repeated measures analysis of variance followed by the least significant difference test.

Figure 2 Effects of EA stimulation on the expressions of PKA-Cβ, p-CREB, BDNF, and TrkB A: PKA-Cβ; B: p-CREB; C: BDNF; D: TrkB. PKA-Cβ: catalytic subunits Cβ of cyclic AMP dependent protein kinase; Normal: control group, Model: injected with PCPA, Shenmen (HT7): model mice with EA at Shenmen (HT7), Baihui (GV20): model mice with EA at Baihui (GV20), Sanyinjiao (SP6): model mice with EA at Sanyinjiao (SP6), Combined: model mice with EA at Shenmen (HT7), Baihui (GV20) and Sanyinjiao (SP6). p-CREB: phosphorylated cAMP-responsive element-binding protein; PCPA: para-chlorophenylalanine; BDNF: brain-derived neurotrophic factor; TrkB: tyrosine kinase receptor B. aP < 0.01, compared with the normal group; bP < 0.05, compared with the model group; cP < 0.05, compared with the Sanyinjiao (SP6) group; dP < 0.01, compared with the model group; eP < 0.05, compared with the Baihui (GV20) group; fP < 0.05, compared with the Shenmen (HT7) group; gP < 0.05, compared with the normal group (n = 6). Data are presented as mean ± standard deviation. Statistics by one-way repeated measures analysis of variance followed by the least significant difference test.

Figure 3 Effects of EA stimulation on the neuronal apoptosis and neurogenesis in the hippocampus (immunofluorescence, × 200, × 100) A: representative images of TUNEL staining (red) and DAPI (blue) in the hippocampal CA1 region to identify apoptotic cells (A1-A6, × 200). A1: normal group; A2: model group; A3: EA-Shenmen (HT7) group; A4: EA-Baihui (GV20) group; A5: EA-Sanyinjiao (SP6) group; A6: EA-combined group. Scale bar: 100 μm. B: representative images of immunofluorescent staining for BrdU (green) and DAPI (blue) in the hippocampal DG regions (B1-B6 is × 100). B1: normal group; B2: model group; B3: EA-Shenmen (HT7) group; B4: EA-Baihui (GV20) group; B5: EA-Sanyinjiao (SP6) group; B6: EA-combined group. Scale bar: 250 μm; C: quantification of TUNEL staining in the sections; D: quantification of BrdU-positive cells in the sections. EA: electroacupuncture; TUNEL: transferase-mediated dUTP-X nick end labeling; DAPI: fluoromount-G with 4',6-diamidino-2-phenylindole; DG: dentate gyrus; BrdU: 5-Bromo-2′-Deoxyuridine. aP < 0.01, compared with the normal group; bP < 0.05, compared with the model group; cP < 0.05, compared with the Shenmen (HT7) group; dP < 0.05, compared with the Baihui (GV20) group; eP < 0.05, compared with the Sanyinjiao (SP6) group；fP < 0.01, compared with the model group; gP < 0.05, compared with the normal group (n = 5). Data are presented as mean ± standard deviation. Statistics by one-way repeated measures analysis of variance followed by the least significant difference test.

Figure 4 Effects of EA at the combined acupoints on spatial memory and learning function, and on hippocampal p-CREB, BDNF, and TrkB expression in the presence of a PKA inhibitor A: escape latency of the four groups in the orientation navigation trial on days 1-4. B: platform crossing times of the four groups in the space exploration trial on day 4. C: representative Western blots of p-CREB, BDNF, TrkB, and the corresponding β-tubulin band. D: densitometric analysis of p-CREB, BDNF, and TrkB protein levels in the normal, model, combined + NS, and combined+H89 groups. Normal: control group; Model: injected with PCPA; combined + NS: model mice with EA at Shenmen (HT7), Baihui (GV20) and Sanyinjiao (SP6) intrahippocampally infused with NS (1 μL/side); combined + H89: model mice with EA at Shenmen (HT7), Baihui (GV20) and Sanyinjiao (SP6) intrahippocampally infused with H89 (5 μmol/L, 1 μL/side). p-CREB: phosphorylated cAMP-responsive element-binding protein; BDNF: brain-derived neurotrophic factor; TrkB: tyrosine kinase receptor B. H89: PKA inhibitor. aP < 0.05, compared with the normal group; bP < 0.05, compared with the model group; cP < 0.01 compared with the normal group; dP < 0.01 compared with the model group; eP < 0.05 compared with the combined + NS group (n = 7). Data are presented as mean ± standard deviation. Statistics by one-way repeated measures analysis of variance followed by the least significant difference test.

References 61

1	Brownlow JA, Miller KE, Gehrman PR. Insomnia and cognitive performance. Sleep Med Clin 2020; 15: 71-6.
2	Schutte-Rodin S, Broch L, Buysse D, Dorsey C, Sateia M. Clinical guideline for the evaluation and management of chronic insomnia in adults. J Clin Sleep Med 2008; 4: 487-504. PMID
3	Tarokh L, Saletin JM, Carskadon MA. Sleep in adolescence: physiology, cognition and mental health. Neurosci Biobehav Rev 2016; 70: 182-8. DOI PMID
4	Abel T, Havekes R, Saletin JM, Walker MP. Sleep, plasticity and memory from molecules to whole-brain networks. Curr Biol 2013; 23: R774-88. DOI URL
5	Kim SM, Zhang S, Park J, et al. REM sleep deprivation impairs learning and memory by decreasing brain O-GlcNAc cycling in mouse. Neurotherapeutics 2021; 18: 2504-17. DOI
6	Edinger JD, Means MK, Carney CE, Krystal AD. Psychomotor performance deficits and their relation to prior nights' sleep among individuals with primary insomnia. Sleep 2008; 31: 599-607. DOI PMID
7	Fortier-Brochu E, Morin CM. Cognitive impairment in individuals with insomnia: clinical significance and correlates. Sleep 2014; 37: 1787-98. DOI PMID
8	Cassilhas RC, Tufik S, de Mello MT. Physical exercise, neuroplasticity, spatial learning and memory. Cell Mol Life Sci 2016; 73: 975-83. DOI PMID
9	Martin SJ, Grimwood PD, Morris RG. Synaptic plasticity and memory: an evaluation of the hypothesis. Annu Rev Neurosci 2000; 23: 649-711. PMID
10	Duffy SN, Craddock KJ, Abel T, Nguyen PV. Environmental enrichment modifies the PKA-dependence of hippocampal LTP and improves hippocampus-dependent memory. Learn Mem 2001; 8: 26-34. DOI URL
11	Kandel ER. The molecular biology of memory: cAMP, PKA, CRE, CREB-1, CREB-2, and CPEB. Mol Brain 2012; 5: 14.
12	Bailey CH, Kande ER, Harris KM. Structural components of synaptic plasticity and memory consolidation. Cold Spring Harb Perspect Biol 2015; 7: a021758. DOI URL
13	Dunning J, During MJ. Molecular mechanisms of learning and memory. Expert Rev Mol Med 2003; 5: 1-11. DOI PMID
14	Nguyen PV, Woo NH. Regulation of hippocampal synaptic plasticity by cyclic AMP-dependent protein kinases. Prog Neurobiol 2003; 71: 401-37. PMID
15	Blitzer RD, Wong T, Nouranifar R, Iyengar R, Landau EM. Postsynaptic cAMP pathway gates early LTP in hippocampal CA1 region. Neuron 1995; 15: 1403-14. PMID
16	Lu Y, Christian K, Lu B. BDNF: a key regulator for protein synthesis-dependent LTP and long-term memory? Neurobiol Learn Mem 2008; 89: 312-23. DOI PMID
17	Drake C, Milner T, Patterson S. Ultrastructural localization of full-length trkB immunoreactivity in rat hippocampus suggests multiple roles in modulating activity-dependent synaptic plasticity. J Neurosci 1999; 19: 8009-26. PMID
18	Han H, Wu LM, Han MX, Yang WM, Wang YX, Fang ZH. Diabetes impairs spatial learning and memory and hippocampal neurogenesis via BDNF in rats with transient global ischemia. Brain Res Bull 2016; 124; 269-77.
19	Stagni F, Giacomini A, Sandra G, et al. A flavonoid agonist of the TrkB receptor for BDNF improves hippocampal neurogenesis and hippocampus-dependent memory in the Ts65Dn mouse model of DS. Exp Neurol 2017; 298: 79-96.
20	Che H, Zhang LY, Ding L, et al. EPA-enriched ethanolamine plasmalogen and EPA-enriched phosphatidylethanolamine enhance BDNF/TrkB/CREB signaling and inhibit neuronal apoptosis in vitro and in vivo. Food Funct 2020; 11: 1729-39. DOI URL
21	Nam MH, Ahn KS, Choi SH. Acupuncture stimulation induces neurogenesis in adult brain. Int Rev Neurobiol 2013; 111: 67-90.
22	Soto-Rodriguez S, Lopez-Armas G, Luquin S, et al. Rapid eye movement sleep deprivation produces long-term detrimental effects in spatial memory and modifies the cellular composition of the subgranular zone. Front Cell Neurosci 2016; 10: 132. DOI PMID
23	Xie G, Huang X, Li H, Wang P, Huang P. Caffeine-related effects on cognitive performance: roles of apoptosis in rat hippocampus following sleep deprivation. Biochem Biophys Res Commun 2021; 534: 632-8. DOI URL
24	Joo EY, Kim H, Suh S, Hong SB. Hippocampal substructural vulnerability to sleep disturbance and cognitive impairment in patients with chronic primary insomnia: magnetic resonance imaging morphometry. Sleep 2014; 37: 1189-98. DOI PMID
25	Xu D, Hang HY, Liu M, et al. Literature study on distribution features of TCM syndromes and syndrome elements of peptic ulcer. Chin J Basic Med Tradit Chin Med 2012; 18: 722-4.
26	Shergis JL, Ni XJ, Jackson ML, et al. A systematic review of acupuncture for sleep quality in people with insomnia. Complement Ther Med 2016; 26: 11-20. DOI PMID
27	Wang H, Liang FX. Thoughts and prospects of research on acupoints compatibility. Zhong Guo Zhen Jiu 2012; 32: 359-62.
28	Qiao LN, Gao QL, Tan LH, et al. Electroacupuncture of multiple acupoints is significantly superior to that of single acupoint in improving sleep by regulating serum sleep-promoting and awakening-promoting factors in insomnia rats. Zhen Ci Yan Jiu 2018; 43: 651-6.
29	Hong J, Chen J, Kan J, Liu M, Yang D. Effects of acupuncture treatment in reducing sleep disorder and gut microbiota alterations in PCPA-Induced insomnia mice. Evid Based Complement Alternat Med 2020; 2020: 3626120.
30	Du CH, Yan Y, Shen CX, Cui XF, Pei XP, Qin XM. Comparative pharmacokinetics of six major compounds in normal and insomnia rats after oral administration of Ziziphi Spinosae Semen aqueous extract. J Pharm Anal 2020; 10: 385-95. DOI PMID
31	Hosseini-Sharifabad A, Ghahremani MH, Sabzevari O, et al. Effects of protein kinase A and G inhibitors on hippocampal cholinergic markers expressions in rolipram- and sildenafil-induced spatial memory improvement. Pharmacol Biochem Behav 2012; 101: 311-9. DOI PMID
32	Wang HL, Liu FL, Li RQ, et al. Electroacupuncture improves learning and memory functions in a rat cerebral ischemia/reperfusion injury model through PI3K/Akt signaling pathway activation. Neural Regen Res 2021; 16: 1011-6. DOI URL
33	Xu H, Zhang YM, Sun H, Chen SH, Si YK. Electroacupuncture at GV20 and ST36 exerts neuroprotective effects via the EPO-Mediated JAK2/STAT3 pathway in cerebral ischemic rats. Evid Based Complement Alternat Med 2017; 2017: 6027421.
34	Hua XB, Li CR, Zhou HL. The development of the rat acupuncture points map. Shi Yan Dong Wu Yu Dong Wu Shi Yan 1991; 1: 1.
35	Chang SC, Ryu Y, FanY, et al. Involvement of the cuneate nucleus in the acupuncture inhibition of drug-seeking behaviors. Front Neurosci 2019; 13: 928. DOI URL
36	Park HJ, Chae Y, Jang J, Shim I, Lee H, Lim S. The effect of acupuncture on anxiety and neuropeptide Y expression in the basolateral amygdala of maternally separated rats. Neurosci Lett 2005; 377: 179-84. DOI URL
37	Chen Y, Zhao Y, Luo DN, Zheng H, Li Y, Zhou SY. Electroacupuncture regulates disorders of gut-brain interaction by decreasing corticotropin-releasing factor in a rat model of IBS. Gastroenterol Res Pract 2019; 2019: 1759842.
38	Wen T, Zhang XF, Liang SX, et al. Electroacupuncture ameliorates cognitive impairment and spontaneous low-frequency brain activity in rats with ischemic stroke. J Stroke Cerebrovasc Dis 2018; 27: 2596-605. DOI PMID
39	Wang RM, Dong Y, Lu YJ, Zhang WL, Brann DW, Zhang QG. Photobiomodulation for global cerebral ischemia: targeting mitochondrial dynamics and functions. Mol Neurobiol 2019; 56: 1852-69. DOI PMID
40	Munoz-Velasco I, Ortiz R, Echeverria OM, Escobar ML, Vazquez-Nin GH. Characterization of the pre-meiotic S phase through incorporation of BrdU during spermatogenesis in the rat. J Histochem Cytochem 2013; 61: 680-9.
41	Shen EY, Chen FJ, Chen YY, Lin MF. Locating the acupoint Baihui (GV20) beneath the cerebral cortex with MRI reconstructed 3D neuroimages. Evid Based Complement Alternat Med 2011; 2011: 362494.
42	Cheong YC, Dix S, Hung Yu Ng E, Ledger WL, Farquhar C. Acupuncture and assisted reproductive technology. Cochrane Database Syst Rev 2013; 7: CD006920.
43	Wang WW, Xie CL, Lu L, Zheng GQ. A systematic review and Meta-analysis of Baihui (GV20)-based scalp acupuncture in experimental ischemic stroke. Sci Rep 2014; 4: 3981. DOI
44	Park S, Lee JH, Yang EJ. Effects of acupuncture on Alzheimer's disease in animal-based research. Evid Based Complement Alternat Med 2017; 2017: 6512520.
45	Wu P, Cheng C, Song XJ, et al. Acupoint combination effect of Shenmen (HT 7) and Sanyinjiao (SP 6) in treating insomnia: study protocol for a randomized controlled trial. Trials 2020; 21: 261. DOI PMID
46	Sakamoto K, Karelina K, Obrietan K. CREB: a multifaceted regulator of neuronal plasticity and protection. J Neurochem 2011; 116: 1-9. DOI PMID
47	Havekes R, Abel T. The tired hippocampus: the molecular impact of sleep deprivation on hippocampal function. Curr Opin Neurobiol 2017; 44: 13-9. DOI PMID
48	Looti Bashiyan M, Nasehi M, Vaseghi S, Khalifeh S. Investigating the effect of crocin on memory deficits induced by total sleep deprivation (TSD) with respect to the BDNF, TrkB and ERK levels in the hippocampus of male Wistar rats. J Psychopharmacol 2021; 35: 744-54. DOI URL
49	Mahboubi S, Nasehi M, Imani A, et al. Benefit effect of REM-sleep deprivation on memory impairment induced by intensive exercise in male wistar rats: with respect to hippocampal BDNF and TrkB. Nat Sci Sleep 2019; 11: 179-88. DOI PMID
50	Guzman-Marin R, Ying Z, Untsova N, et al. Suppression of hippocampal plasticity-related gene expression by sleep deprivation in rats. J Physiol 2006; 575: 807-19. DOI URL
51	Han XH, Zhao XX, Lu M, et al. Electroacupuncture ameliorates learning and memory via activation of the CREB signaling pathway in the hippocampus to attenuate apoptosis after cerebral hypoperfusion. Evid Based Complement Alternat Med 2013; 2013: 156489.
52	Li XH, Chen C, Yang XP, et al. Acupuncture improved neurological recovery after traumatic brain injury by activating BDNF/TrkB Pathway. Evid Based Complement Alternat Med 2017; 2017: 8460145.
53	Santin LJ, Rubio S, Begega A, Miranda R, Arias JL. Spatial learning and the hippocampus. Rev Neurol 2000; 31: 455-62.
54	van Praag H, Shubert T, Zhao C, Gage FH. Exercise enhances learning and hippocampal neurogenesis in aged mice. J Neurosci 2005; 25: 8680-5. DOI PMID
55	Cao L, Jiao XY, Zuzga D, et al. VEGF links hippocampal activity with neurogenesis, learning and memory. Nat Genet 2004; 36: 827-35. DOI PMID
56	Jia Z, Geng L, Xie G, Chu Q, Zhang W. Sevoflurane impairs acquisition learning and memory function in transgenic mice model of Alzheimer's disease by induction of hippocampal neuron apoptosis. Int J Clin Exp Med 2015; 8: 15490-7. PMID
57	Mori K, Yoshioka M, Suda N, et al. An incomplete cerebral ischemia produced a delayed dysfunction in the rat hippocampal system. Brain Res 1998; 795: 221-6. DOI PMID
58	McDermott CM, LaHoste GL, Chen C, Musto A, Bazan NG, Magee JC. Sleep deprivation causes behavioral, synaptic, and membrane excitability alterations in hippocampal neurons. J Neurosci 2003; 23: 9687-95. PMID
59	Ye S, Xie DJ, Zhou P, et al. Huangpu Tongqiao formula ameliorates the hippocampus apoptosis in diabetic cognitive dysfunction mice by activating CREB/BDNF/TrkB signaling pathway. Evid Based Complement Alternat Med 2021; 2021: 5514175.
60	Feng SF, Wang Q, Wang HN, et al. Electroacupuncture pretreatment ameliorates hypergravity-induced impairment of learning and memory and apoptosis of hippocampal neurons in rats. Neurosci Lett 2010; 478: 150-5. DOI PMID
61	Li XY, Guo F, Zhang QM, et al. Electroacupuncture decreases cognitive impairment and promotes neurogenesis in the APP/PS 1 transgenic mice. BMC Complement Altern Med 2014; 14: 37. DOI URL

[1]	LIU Tingting, LIU Tongou, LIU Mingfu. Effectiveness and safety of acupuncture in treatment of pregnancy-related symptoms: a systematic review and Meta-analysis [J]. Journal of Traditional Chinese Medicine, 2024, 44(1): 16-26.
[2]	WANG Kun, ZHOU Jie, CUI Shuai, WU Xin, ZHU Guoqi, WU Shengbing, ZHOU Meiqi. Electroacupuncture ameliorates cardiac dysfunction in myocardial ischemia model rats: a potential role of the hypothalamic-pituitary-adrenal axis [J]. Journal of Traditional Chinese Medicine, 2023, 43(5): 944-954.
[3]	HUANG Heyin, WANG Yichen, ZHANG Qinxiu, WU Xiaojuan, WANG Jiang, Li Xiangyu, PANG Rui, FAN Li, CAO Liu, TANG Luo. Efficacy of catgut embedding in Baihui (GV20) and Feishu (BL13) and Pishu (BL20) on lung tissue, brain tissue and blood related indexes in rats with allergic rhinitis of lung deficiency type [J]. Journal of Traditional Chinese Medicine, 2023, 43(5): 973-982.
[4]	HUANG Hongye, WANG Bingqian, CHEN Shuijin, FANG Jiayu, WANG Xiaohua, CHEN Lechun, JIANG Yu, ZHANG Huanzhen, CHEN Jincheng, LIN Zhigang. Chinese Tuina remodels the synaptic structure in neuropathic pain rats by downregulating the expression of N-methyl D-aspartate receptor subtype 2B and postsynaptic density protein-95 in the spinal cord dorsal horn [J]. Journal of Traditional Chinese Medicine, 2023, 43(4): 715-724.
[5]	LI Xingjie, LIU Qiqi, XIA Rui, LIU Jun, WANG Dan, SHI Jiao, KUANG Yuxing, DAI Yalan, HUANG Haoyu, TANG Wei, CHEN Shangjie. Moxibustion modulates working memory in patients with amnestic mild cognitive impairment: a functional magnetic resonance imaging study [J]. Journal of Traditional Chinese Medicine, 2023, 43(4): 801-808.
[6]	MA Fangfang, ZHANG Hewei, LI Bingxue, CHENG Peiyu, YU Mingwei, WANG Xiaomin. Acupuncture and moxibustion for malignant tumor patients with psychological symptoms of insomnia, anxiety and depression: a systematic review and Meta-analysis [J]. Journal of Traditional Chinese Medicine, 2023, 43(3): 441-456.
[7]	YE Yujuan, WEI Yuting, JIA Jing, YAN Xingke. Efficacy of needling Baihui (GV20), Neiguan (PC6), Shenmen (HT7) and Taichong (LR3) on cerebral cortical blood oxygen level in rats with insomnia [J]. Journal of Traditional Chinese Medicine, 2023, 43(3): 523-532.
[8]	XIN Zhixiong, LI Jiyuan, XU Yanni, LING Jing, JIANG Min, YU Yutian. Acupuncture on intrauterine growth restriction associated brain injury: case study including use of magnetic resonance imaging [J]. Journal of Traditional Chinese Medicine, 2023, 43(3): 602-605.
[9]	QU Dongxiao, GE Yiqin, ZHUO Limin, CHEN Liji, XUE Yonghua, CHENG Jiwei, TAO Jie, LI Guoyi, ZHU Yudan, XIAO Qian. Efficacy and mechanisms of Dingxian pill (定痫丸) combined with valproic acid on pentylenetetrazol-induced chronic epilepsy in rats [J]. Journal of Traditional Chinese Medicine, 2023, 43(2): 286-294.
[10]	WANG Bochuan, ZHANG Yong, ZHANG Qiuyun, ZHANG Zhiqiang, LUO Changyong, WANG Zhendong, BAI Chen, WANG Yuhan, GE Xueyi, QIAN Ying, YU He, GU Xiaohong. Reveal the mechanisms of prescriptions for liver cancer' treatment based on two illustrious senior TCM physicians [J]. Journal of Traditional Chinese Medicine, 2023, 43(1): 188-197.
[11]	TIAN Meijing, HE Yannan, ZHENG Mingcui, QIN Gaofeng, GONG Zhuoyan, HUANG Shuaiyang, WANG Pengwen. Chinese herbal compound Jinsiwei (金思维) improves synaptic plasticity in mice with sporadic Alzheimer’s disease induced by streptozotocin [J]. Journal of Traditional Chinese Medicine, 2023, 43(1): 78-86.
[12]	YAN Bin, WANG Jingbo, TIAN Guoqing. Efficacy of quercetin, oleanolic acid, icariin on apoptosis and mitogen-activated protein kinases signaling pathways in hippocampal neurons of Sprague-Dawley rats cultured with high glucose medium [J]. Journal of Traditional Chinese Medicine, 2021, 41(5): 732-738.
[13]	PIAO Xiang, WANG Wei, CHEN Hanjiang, YAN Rong, LI Mengquan. Effect of Rongchang capsule (茸菖胶囊) on seizure behavior,cognitive impairment,and hippocampal DNA damage and inflammatory factors in epileptic rats [J]. Journal of Traditional Chinese Medicine, 2021, 41(3): 438-446.
[14]	QIN Xiude, LIU Yu, WU Yanqing, WANG Shuo, WU Haibin, ZHU Jinqiang. Anti-apoptotic efficacy of Qingnao Yizhi formula(清脑益智方) in hypoxia/reoxygenation primary cortical neurons through the promotion of synaptic plasticity by modulating the NogoA-Nogo receptor/Rho-Rho kinase signaling pathway [J]. Journal of Traditional Chinese Medicine, 2021, 41(1): 59-67.
[15]	Wang Xu, Li Zhaolong, Li Chunri, Wang Yue, Yu Song, Ren Lu. Electroacupuncture with Bushen Jiannao improves cognitive deficits in senescence-accelerated mouse prone 8 mice by inhibiting neuroinflammation [J]. Journal of Traditional Chinese Medicine, 2020, 40(5): 812-819.

Home

Online First

Author Center

Reviewer Center

Issues

Announcement

About Us