Electro-Acupuncture Improve the Early Pattern Separation in Alzheimer’s Disease Mice via Basal Forebrain-Hippocampus Cholinergic Neural Circuit

Li, Long; Li, Jianhong; Dai, Yaling; Yang, Minguang; Liang, Shengxiang; Wang, Zhifu; Li, Weilin; Chen, Lidian; Tao, Jing

doi:10.3389/fnagi.2021.770948

Cited by 17 publications

(19 citation statements)

References 50 publications

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“…Our previous study revealed that EA at DU20 and DU24 acupoints could ameliorate cognitive dysfunction in AD model mice. 23,46 EA treatment could inhibit hippocampal Aβ deposition and abnormal phosphorylation of the tau protein, and enhance glucose metabolism in AD model mice. 47,48 Additionally, several studies have reported that EA treatment exerts its therapeutic effects on cognition by regulating basal forebrain hippocampal circuit physiology.…”

Section: Discussionmentioning

confidence: 97%

Electroacupuncture regulates Rab5a‐mediating NGF transduction to improve learning and memory ability in the early stage of AD mice

Li,

Yang,

Dai

et al. 2024

CNS Neurosci Ther

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AimsNerve growth factor (NGF) loss is a potential factor for the degeneration of basal forebrain cholinergic neurons (BFCNs) in Alzheimer's disease (AD), and Rab5a is a key regulatory molecule of NGF signaling transduction. Here, we investigated the changes of Rab5a in 5 × FAD mice and further explored the mechanism of Electroacupuncture (EA) treatment in improving cognition in the early stage of AD.MethodsThe total Rab5a and Rab5a‐GTP in 5‐month‐old 5 × FAD mice and wild‐type mice were detected using WB and IP technologies. 5 × FAD mice were treated with EA at the Bai hui (DU20) and Shen ting (DU24) acupoints for 4 weeks and CRE/LOXP technology was used to confirm the role of Rab5a in AD mediated by EA stimulation. The Novel Object Recognition and Morris water maze tests were used to evaluate the cognitive function of 5 × FAD mice. The Nissl, immunohistochemistry, and Thioflavin S staining were used to observe pathological morphological changes in the basal forebrain circuit. The Golgi staining was used to investigate the synaptic plasticity of the basal forebrain circuit and WB technology was used to detect the expression levels of cholinergic‐related and NGF signal‐related proteins.ResultsThe total Rab5a was unaltered, but Rab5a‐GTP increased and the rab5a‐positive early endosomes appeared enlarged in the hippocampus of 5 × FAD mice. Notably, EA reduced Rab5a‐GTP in the hippocampus in the early stage of 5 × FAD mice. EA could improve object recognition memory and spatial learning memory by reducing Rab5a activity in the early stage of 5 × FAD mice. Moreover, EA could reduce Rab5a activity to increase NGF transduction and increase the levels of phosphorylated TrkA, AKT, and ERK in the basal forebrain and hippocampus, and increase the expression of cholinergic‐related proteins, such as ChAT, vAchT, ChT1, m1AchR, and m2AchR in the basal forebrain and ChAT, m1AchR, and m2AchR in the hippocampus, improving synaptic plasticity in the basal forebrain hippocampal circuit in the early stage of 5 × FAD mice.ConclusionsRab5a hyperactivation is an early pathological manifestation of 5 × FAD mice. EA could suppress Rab5a‐GTP to promote the transduction of NGF signaling, and enhance the synaptic plasticity of the basal forebrain hippocampal circuit improving cognitive impairment in the early stage of 5 × FAD mice.

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Section: Discussionmentioning

confidence: 97%

Electroacupuncture regulates Rab5a‐mediating NGF transduction to improve learning and memory ability in the early stage of AD mice

Li,

Yang,

Dai

et al. 2024

CNS Neurosci Ther

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“…An interesting finding was that the number of M1-type muscarinic acetylcholine receptors (M1 mAChR) in the medial septum (MS)/vertical limb of the diagonal band of Broca (VDB)-DG region increased after 2/20 Hz EA treatment at GV20 and GV24, with an increase in DCX + cells and Neuro-D1 + cells, however, the above effects of EA vanished when hM4Di Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) were used to block cholinergic circuits in this area. This evidence revealed that M1 mAChR may also facilitate EA-induced neuronal regeneration in the MS/VDB-DG region, although further research is required to confirm this hypothesis [ 102 ].…”

Section: Methodsmentioning

confidence: 92%

“…Lee et al reported that acupuncture at GV20 improved cognitive dysfunction induced by scopolamine, alleviated the decline in hippocampal ChAT levels, and restored the expression of the hippocampal choline transporter 1 and vesicular acetylcholine transporter [ 135 ], suggesting that acupuncture may regulate ACh metabolism, and may contribute to the circulation of choline from the synaptic cleft back to the presynaptic terminal, and improve the efficiency of vesicle filling. Li et al reported that 2/20 Hz EA at GV20 and GV24 improved pattern separation disorders in 5xFAD mice, up-regulated ChAT and vesicular acetylcholine transporter, and down-regulated AChE in the MS/VDB-DG region, while the use of hM4Di DREADDs reversed the above effects of EA, suggesting that EA may improve early pattern separation by activating cholinergic system in MS/VDB-DG [ 102 ]. According to the reported study of Liu et al, 2/100 Hz EA at GV20, PC6, and LI4 could enhance learning and memory in rats with postoperative cognitive impairment, as well as upregulate α7nAChR + neurons in the hippocampus regions [ 136 ].…”

Section: Methodsmentioning

confidence: 99%

The neuroprotective and neural circuit mechanisms of acupoint stimulation for cognitive impairment

et al. 2023

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Cognitive impairment is a prevalent neurological disorder that burdens families and the healthcare system. Current conventional therapies for cognitive impairment, such as cholinesterase inhibitors and N-methyl-d-aspartate receptor antagonists, are unable to completely stop or reverse the progression of the disease. Also, these medicines may cause serious problems with the digestive system, cardiovascular system, and sleep. Clinically, stimulation of acupoints has the potential to ameliorate the common symptoms of a variety of cognitive disorders, such as memory deficit, language dysfunction, executive dysfunction, reduced ability to live independently, etc. There are common acupoint stimulation mechanisms for treating various types of cognitive impairment, but few systematic analyses of the underlying mechanisms in this domain have been performed. This study comprehensively reviewed the basic research from the last 20 years and found that acupoint stimulation can effectively improve the spatial learning and memory of animals. The common mechanism may be that acupoint stimulation protects hippocampal neurons by preventing apoptosis and scavenging toxic proteins. Additionally, acupoint stimulation has antioxidant and anti-inflammatory effects, promoting neural regeneration, regulating synaptic plasticity, and normalizing neural circuits by restoring brain functional activity and connectivity. Acupoint stimulation also inhibits the production of amyloid β-peptide and the phosphorylation of Tau protein, suggesting that it may protect neurons by promoting correct protein folding and regulating the degradation of toxic proteins via the autophagy-lysosomal pathway. However, the benefits of acupoint stimulation still need to be further explored in more high-quality studies in the future.

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“…The nonacupoint (Non-acu) group used for the nonacupoints (on the lower part of the bilateral flank, 3 mm obliquely downward) was subjected to stimulation with the same parameters. The sham operation and 2VO groups were grasped under the same conditions and then returned to their cages for rearing [ 29 ].…”

Section: Methodsmentioning

confidence: 99%

Electroacupuncture Increases the Hippocampal Synaptic Transmission Efficiency and Long-Term Plasticity to Improve Vascular Cognitive Impairment

Dai

Zhang

Yang

et al. 2022

Mediators of Inflammation

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Studies have shown that electroacupuncture (EA) can effectively improve vascular cognitive impairment (VCI), but its mechanisms have not been clearly elucidated. This study is aimed at investigating the mechanisms underlying the effects of EA treatment on hippocampal synaptic transmission efficiency and plasticity in rats with VCI. Methods. Sprague–Dawley rats were subjected to VCI with bilateral common carotid occlusion (2VO). EA stimulation was applied to Baihui (GV20) and Shenting (GV24) acupoints for 30 min once a day, five times a week, for four weeks. Our study also included nonacupoint groups to confirm the specificity of EA therapy. The Morris water maze (MWM) was used to assess cognitive function. Electrophysiological techniques were used to detect the field characteristics of the hippocampal CA3–CA1 circuit in each group of rats, including input-output (I/O), paired-pulse facilitation ratios (PPR), field excitatory postsynaptic potential (fEPSP), and excitatory postsynaptic current (EPSC). The expression of synapse- and calcium-mediated signal transduction associated proteins was detected through western blotting. Results. The MWM behavioural results showed that EA significantly improved cognitive function in VCI model rats. EA increased the I/O curve of VCI model rats from 20 to 90 μA. No significant differences were observed in hippocampal PPR. The fEPSP of the hippocampal CA3–CA1 circuit was significantly increased after EA treatment compared with that after nonacupuncture treatment. We found that EA led to an increase in the EPSC amplitude and frequency, especially in the decay and rise times. In addition, the protein expression and phosphorylation levels of N-methyl-D-aspartate receptor 2B, α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor 1, and Ca2+-calmodulin-dependent protein kinase II increased to varying degrees in the hippocampus of VCI model rats. Conclusion. EA at GV20 and GV24 acupoints increased the basic synaptic transmission efficiency and synaptic plasticity of the hippocampal CA3–CA1 circuit, thereby improving learning and memory ability in rats with VCI.

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Electro-Acupuncture Improve the Early Pattern Separation in Alzheimer’s Disease Mice via Basal Forebrain-Hippocampus Cholinergic Neural Circuit

Cited by 17 publications

References 50 publications

Electroacupuncture regulates Rab5a‐mediating NGF transduction to improve learning and memory ability in the early stage of AD mice

Electroacupuncture regulates Rab5a‐mediating NGF transduction to improve learning and memory ability in the early stage of AD mice

The neuroprotective and neural circuit mechanisms of acupoint stimulation for cognitive impairment

Electroacupuncture Increases the Hippocampal Synaptic Transmission Efficiency and Long-Term Plasticity to Improve Vascular Cognitive Impairment

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