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Exploring the mechanism of pre-electroacupuncture at " Neiguan" (PC6) and " Jianshi" (PC5) acupoints on learning, memory, and locus coeruleus-hippocampal neural circuit in Alzheimer′s disease-like rats via the β2AR/β-arrestin2/NF-κB pathway

  • role： First author第一作者
  • Affiliation：

    College of Acupuncture-Moxibustion and Orthopaedics-Traumatology, Hubei University of Chinese Medicine, Wuhan 430061, China

    Hubei Shizhen Laboratory, Wuhan 430061, China

  • Introduction：何川，男，博士，讲师
HE Chuan12,  
  • Affiliation：

    College of Acupuncture-Moxibustion and Orthopaedics-Traumatology, Hubei University of Chinese Medicine, Wuhan 430061, China

    Hubei Shizhen Laboratory, Wuhan 430061, China

WANG Li12,  
  • Affiliation：

    College of Acupuncture-Moxibustion and Orthopaedics-Traumatology, Hubei University of Chinese Medicine, Wuhan 430061, China

    Hubei Shizhen Laboratory, Wuhan 430061, China

PAN Xiaoli12,  
  • Affiliation：

    Shenzhen Traditional Chinese Medicine Hospital, Shenzhen 518033, China

    The Fourth Clinical College of Guangzhou University of Chinese Medicine, Shenzhen 518033, China

YU Chaochao34,  
  • Affiliation：

    College of Acupuncture-Moxibustion and Orthopaedics-Traumatology, Hubei University of Chinese Medicine, Wuhan 430061, China

    Hubei Shizhen Laboratory, Wuhan 430061, China

XIAO Juan12,  
  • Affiliation：

    College of Acupuncture-Moxibustion and Orthopaedics-Traumatology, Hubei University of Chinese Medicine, Wuhan 430061, China

    Hubei Shizhen Laboratory, Wuhan 430061, China

LU Zhenkun12,  
  • Affiliation：

    College of Acupuncture-Moxibustion and Orthopaedics-Traumatology, Hubei University of Chinese Medicine, Wuhan 430061, China

    Hubei Shizhen Laboratory, Wuhan 430061, China

LI Xiangyu12,  
  • Affiliation：

    College of Acupuncture-Moxibustion and Orthopaedics-Traumatology, Hubei University of Chinese Medicine, Wuhan 430061, China

    Hubei Shizhen Laboratory, Wuhan 430061, China

DU Yanjun12,  
  • role： Corresponding author通信作者
  • Affiliation：

    College of Acupuncture-Moxibustion and Orthopaedics-Traumatology, Hubei University of Chinese Medicine, Wuhan 430061, China

    Hubei Shizhen Laboratory, Wuhan 430061, China

    Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan 430061, China

  • Email：40052958@qq.com
  • Introduction：Prof. SHEN Feng, Ph.D., Chief Physician, Doctoral Supervisor. Hubei University of Chinese Medicine, No.1, West Huangjiahu Road, Hongshan District, Wuhan 430061. E-mail: 40052958@qq.com
SHEN Feng125*

реферат

ObjectiveTo investigate the effects of pre-electroacupuncture (EA) on spatial learning and memory, the locus coeruleus-hippocampal neural circuit, and neuroinflammation in Alzheimer′s disease (AD)-like rats, and to explore the possible mechanism of pre-EA in preventing and treating AD.MethodsThirty-six male SD rats were divided into the normal, model, EA, and sham EA groups using the random number table method, with nine rats per group. An AD-like rat model was prepared through intraperitoneal injection of 120 mg/(kg·d) D-galactose for eight consecutive weeks. After daily intraperitoneal injection, the rats in the EA group underwent EA stimulation at the " Neiguan" (PC6) and " Jianshi" (PC5) acupoints with a continuous wave, frequency of 50 Hz, and a current of 1 mA for 20 min once a day for 8 weeks. The sham EA group was only superficially punctured to the subcutaneous tissue at the " Neiguan" (PC6) and " Jianshi" (PC5) acupoints without electricity, and the rest of the operations were the same as those in the EA group. The Morris water maze experiment was then used to evaluate the spatial learning and memory of the rats. Immunofluorescence labeling was used to detect dopamine β hydroxylase and c-Fos co-localization in the locus coeruleus of noradrenergic neurons, as well as glial fibrillary acidic protein and tumor necrosis factor-α (TNF-α) co-localization in the CA1 area of the hippocampus of astrocytes. Western blotting was used to measure the protein expressions of norepinephrine (NE), β2-adrenergic receptor (β2AR), β-inhibitory protein 2 (β-arrestin2), nuclear transcription factor-κB (NF-κB) inhibitory factor protein α (IκBα), and NF-κB in the hippocampus of rats. An enzyme-linked immunosorbent assay was used to detect the TNF-α, interleukin-1β (IL-1β), and interleukin-6 (IL-6) contents in hippocampal tissue.ResultsCompared with the normal group, the average escape latency of the model group rats was prolonged, and the times of crossing platform and exploration time in the target quadrant were reduced (P<0.01), while the EA intervention can shorten the average escape latency and increase the times of crossing platform and exploration time in the target quadrant (P<0.01). Compared with the normal group, the expression of co-located noradrenergic neurons in the model group decreased, co-located astrocytes increased (P<0.01); NE, β2AR, β-arrestin2, and IκBα protein expression decreased(P<0.01), NF-κB protein expression increased (P<0.01); the contents of TNF-α, IL-1β, and IL-6 increased (P<0.01). Compared with the model group, the EA group showed an increase in the expression of co-located noradrenergic neurons, a decrease in co-located astrocytes (P<0.01), an increase in NE, β2AR, β-arrestin2, and IκBα protein expressions (P<0.01), a decrease in NF-κB protein expression (P<0.01), and a decrease in TNF-α, IL-1β, and IL-6 levels (P<0.01). No significant difference was observed in the above indicators between the model and sham EA groups.ConclusionPre-EA at " Neiguan" (PC6) and " Jianshi" (PC5) can alleviate learning and memory dysfunction, alleviate noradrenergic neuronal loss in the locus coeruleus, inhibit astrocyte activation, protect the locus coeruleus-hippocampal neural circuit, and may be associated with inhibiting β2AR/β-arrestin2/NF-κB inflammatory pathway activation.

ключеви́че слова́

Alzheimer′s disease;pre-electroacupuncture;locus coeruleus;β2 adrenergic receptor/β-inhibitory protein 2/nuclear transcription factor kappa B pathway;neuroinflammation;rats

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