Table 2.
The effect and mechanisms of acupuncture on cognitive disorders in neurodegenerative diseases.
| Author | Animal model/participant | Acupoint | Acupuncture type | Acupuncture session | Behavioral test | Outcomes |
|---|---|---|---|---|---|---|
| Glutamatergic system | ||||||
| He et al. (2022) | METH withdrawal mice model of spatial memory impairment | GV29, GV20 | EA, 200 Hz with 1–2 mA, 30 min/day | 14 days | MWM: time in probe test↓; time in OLM test↑ | dCA1: extracellular Glu↓, c-Fos-positive neurons↓; C3-positive astrocytes↓, reactive astrocytes↓, C3 protein↓, GLT-1-positive astrocytes↑, GLT-1 protein↑; Schaffer projections from dCA3 to dCA1: number of c-Fos-positive presynaptic neurons#, VGLUT-1-positive staining# |
| Hou et al. (2022) | SAMP8 mice model of AD | GV20, ST36 | EA,1 mA, 10 Hz, 30 min/day | 14 days | Y Maze Test: correct spontaneous alternation rate↑; MWM test: movement paths↓, escape latency↓, percentage of time spent in target quadrant↑, number of platform crossings↑ | CSF: OxA↓, Glu↓; hippocampus: Nissl bodies (CA1, CA3)↑; OxA protein (hippocampus, lateral hypothalamus)↓, cAMP↑, pPKA/PKA↑, pCREB/CREB↑, GluN1↑, GluN2A↑, GluA2↑, SYP↑, PSD95 ↑, number of synapse↑, synaptic density↑ |
| Lin et al. (2018) | APP/PS1 transgenic mice model of AD | GV20 | EA, 100 Hz, 1/20 mA, 30 min/day | 6 days/week, 4 weeks | Escape latency↓, number of mice crossing the platform↑ Step-down avoidance test: latency↑, number of errors↓ |
Left hippocampus: NAA/Cr↑, Glu/Cr↑; hippocampus, CA1 and CA3 areas: surviving neurons↑; hippocampus: BDNF↑, TrkB↑ |
| GABAergic system | ||||||
| Li et al. (2023) | 5xFAD mice model of AD | GV20, GV14 | EA, 2 Hz, 1 mA, 30 min/day | 5 days | MWM test: escape latency↓ NOR task: time↑ |
Hippocampus: gephyrin protein↑, synapsin 1#, PSD95#, GAD65↑, SST↑, PV#; dorsal CA1: CR↑ cell↑, sIPSCs frequency↑, sEPSCs frequency↑, sEPSCs area↑, sEPSCs amplitude#, charge ratio of sEPSC/sIPSC↓, theta oscillation↑, gamma oscillation↑; dorsal hippocampus: SST+ cell↑ |
| Serotonergic system | ||||||
| Xiao et al. (2023) | D-galactose induced rat model of AD | GV20, ST36 | EA, 50 Hz, 1 mA, 20 min/day | once a day, 8 weeks | MWM test: escape latency↓, exploration time↑ | colon: 5-HT levels↓, Trp↑ hippocampus: 5-HT levels↑, Trp↑, 5-HT6R↓, JNK↓, p-JUNK↓, c-JUN↓, p-c-Jun↓ |
| Cholinergic system | ||||||
| Li et al. (2022) | 5xFAD mice model of AD | GV 20, GV 14 | EA, 2/20 Hz, 1 mA, 30 min/day | 5 days/week, 4 weeks | OFT#: traveled distance, average speed, time spent in the central part; NOR#: object exploration; Novel location recognition: location exploration↑; Location discrimination task: Must touch training trials#, PIT accuracy#, LDR trials↓ |
MS/VDB: NAA/Cr↑, Cho/Cr↑; AChE↓, VAChT↑, Aβ fraction ratio↓# DG: NAA/Cr↑, Cho/Cr↑; DG, MOD of AChE#, MOD of VAChT#, ChAT↑, Aβ fraction ratio↓, M1+ cell↑ hippocampus: DCX+ cell↑, Neuro-D1+ cell↑ |
| Lee et al. (2014) | Scopolamine induced rat model of memory impairment | GV20 | MA | - | MWM test: escape latency↓ | Hippocampus: ChAT↑, BDNF↑, CREB↑, CHT1↑, VAChT↑, BDNF mRNA↑, CREB mRNA↑ |
| Lee et al. (2012) | Corticosterone induced rat model of spatial cognitive impairment | HT7/TE5 | MA | - | MWM test: escape latency↓; OFT: line crossing number# |
Hippocampus: cholinergic neurons↑, BDNF mRNA↑, CREB mRNA↑ hippocampal CA1 area: ChAT-immunopositive neuron↑, AchE-immunopositive fibers↑; hippocampal CA3 area: AchE-immunopositive fibers↑; Medial septum: ChAT-immunopositive neuron numbers↑ |
| Glial cells | ||||||
| Xie et al. (2021) | Aβ1-42 induced rat model of AD | GV20 | EA, 10 mA, 20 Hz, 30 min/day | 6 times/week, 3 weeks | MWM test: escape latency↓, swimming speed↑, swimming distance↓, probe times of trails↑ | CA1: activation of astrocytes↓, Iba1+ iNOS+ cell↓, Iba1+ Arg1+ cell↑, GFAP+ IL-1β+ cell↓, GFAP+ TNF-α+ cell↓, GFAP+ IL-6 cell↓, Iba1+ IL-4+ cell↑, Iba1+ IL-10+ cell↑, GFAP+ IL-4+ cell↑, GFAP+ IL-10 cell↑, Iba1+ p65+ cell↓, GFAP+ p65+ cell↓, Iba1+ STAT6+ cell↑, STAT6 mRNA expression↑; DG: activation of astrocytes↓, Iba1+ iNOS+ cell↓, Iba1+ Arg1+ cell↑, IL-1β-#, TNF-α↓#, Iba1+ IL-6+ cell#, GFAP+ IL-1β+ cell↓, GFAP+ TNF-α+ cell↓, GFAP+ IL-6+ cell↓, Iba1+ IL-4+ cell↑, Iba1+ IL-10+ cell↑, GFAP+ IL-4+ cell↑, GFAP+ IL-10 cell↑, GFAP+ p65+ cell↓, Iba1+ STAT6+ cell↑, STAT6 mRNA expression↑ |
| Li M. et al. (2020) | SAMP8 mice model of AD | GV20, GV29 | EA, 2 Hz, 0.1 mA, 15 min/day | once a day, 15 days | MWM test: escape latency↓, platform crossing number↑ | Hippocampus: TREM2 protein↑ |
| Wang et al. (2020) | SAMP8 mice model of AD | GV29, LI20 | EA, 15 Hz, 1.5 mA, 10 min/day | 6 days/week, 4 weeks | MWM test: escape latency↓, path length of place navigation trial↓, swimming time↑ |
Hippocampus: Aβ protein↓, hyperphosphorylated tau proteins↓, P-tau/tau↓#, integrated density of Iba1+ cell↓, activated microglia area↓; CA1: SYP expression content↑ |
| Cai et al. (2019) | 5xFAD mice model of AD | KI3 | EA, 1 mA, 2 Hz, 15 min/day | 3 times/week, 2 weeks | NOR test: percentage of exploration time of the novel object↑; Y maze test: spontaneous alternations↑ |
Frontal cortex: mean glucose level↑; prefrontal cortex: CD11b↓, GFAP↓, COX2↓, HO-1↓, transferrin↓, Bax↓, LTP↑, synaptophysin, PSD-95↑, synaptic structures↑, APP↓, APOE↓#, BACE↓#, Aβ1–42 levels↓, CD68+ cell/Aβ plaque↓; cortex: mean glucose level↑; hippocampus: mean glucose level#, LTP↑; hypothalamus: mean glucose level↑ |
| Tang et al. (2019) | Aβ1-42 induced rat model of AD | GV20, BL23 | MA, 20 min/day | once a day, 8 weeks | MWM test: escape latency↓, platform crossing number↑ | Hippocampal dentate gyrus: neuronal edema↓, astrocytes edema↓ |
| Wang et al. (2014) | APP/PS1 transgenic mice model of AD | GV20 | EA, 2/15 Hz, 1 mA, 30 min/day | 5 days/week, 4 weeks | MWM test: escape latency↓, swimming speed#, time spent in the target quadrant↑ | GFAP↓, NDRG2↓ |
| Han et al. (2018) | LPS-induced mice model of cognitive impairment | GV20 | EA, 2/100 Hz, 4 mA, 30 min/day | 7 days | MWM test: escape latency↓, platform crossing number↑ | Hippocampus: α7nAChR positive neurons↑, ACh content↑, ChAT↑, AChE activities↓, MDA↓, H2O2↓, CAT activity↑, GSH content↑, IL-1β↓, IL-6↓, TNF-α↓ |
#p > 0.05; 5 × FAD, five familial Alzheimer’s disease; α7nAChR, α7 nicotinic acetylcholine receptors; Aβ, amyloid-β; ACh, acetylcholine; AD, Alzheimer’s disease; APOE, apolipoprotein E; APP/PS1, amyloid precursor protein/presenili1; Arg1, M2 marker Arginase 1; BACE, β-site amyloid precursor protein cleaving enzyme 1; Bax, Bcl-2-associated X; BDNF, brain-derived neurotrophic factor; C3, compliment component 3; cAMP, cyclic adenosine monophosphate; CAT, catalase; CD11b, cluster of differentiation 11b; Cho, Choline; Cr, creatine; CREB, cAMP response element-binding protein; CSF, cerebrospinal fluid; COX2, cyclooxygenase 2; dCA1, dorsal CA1; EA, electricacupuncture; GABA, γ-aminobutyric acid; GFAP, glial fibrillary acidic protein; GLT-1, glutamate transporter 1; Glu, glutamine; GSH, glutathione; H2O2, hydrogen peroxide; IL, interleukin; iNOS, inducible nitric oxide synthase inos; LDT, Location Discrimination Task; LPS, lipopolysaccharide; LTP, long-term potentiation; MA, manual acupuncture; MDA, malondialdehyde; MEPs, Motor-Evoked Potentials; MFB, medial forebrain bundle; mGluR3, metabotropic glutamate receptor 3; MRI, Magnetic Resonance Imaging; MS/VDB-DG, medial septal and vertical limb of the diagonal band and dentate gyrus; mTOR, mammalian target of rapamycin; MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; MWM, Morris water maze; NAA, N-acetylaspartate; NG2, nerve/glial antigen 2; NDRG2, N-myc downstream-regulated gene 2; NeuN, neuron-specific nuclear protein; NLR, Novel Location Recognition; NOR, novel object recognition; OFT, Open Field Test; OLM, object location memory; ORT, Object Recognition Test; OxA, Orexin A; pCREB, phosphorylated CREB; PIT, punish incorrect training; PKA, cAMP response element-binding protein; PSD95, postsynaptic density protein 95; PV, parvalbumin; SAMP8, senescence-accelerated mice prone 8; sEPSCs, spontaneous excitatory postsynaptic currents; SST, somatostatin; STAT6, signal transducer and activator of transcription 6; STN, subthalamic nucleus; SYP, synaptophysin; TREM2, triggering receptors expressed on myeloid cells 2; Trp, tryptophan; TrkB, Tyrosine Kinase receptor B; VAChT, vesicular acetylcholine transporter; VGLUT-1, vesicular Glu transporter 1.