Electroacupuncture Improves Blood-Brain Barrier and Hippocampal Neuroinflammation in SAMP8 Mice by Inhibiting HMGB1/TLR4 and RAGE/NADPH Signaling Pathways

WANG Yuan; WANG Qiang; LUO Di; ZHAO Pu; ZHONG Sha-sha; DAI Biao; WANG Jia-ju; WAN Yi-tong; LIU Zhi-bin; YANG Huan

doi:10.1007/s11655-023-3592-5

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Electroacupuncture Improves Blood-Brain Barrier and Hippocampal Neuroinflammation in SAMP8 Mice by Inhibiting HMGB1/TLR4 and RAGE/NADPH Signaling Pathways

Acupuncture Research | Updated：2023-04-27

- Electroacupuncture Improves Blood-Brain Barrier and Hippocampal Neuroinflammation in SAMP8 Mice by Inhibiting HMGB1/TLR4 and RAGE/NADPH Signaling Pathways
- Electroacupuncture Improves Blood-Brain Barrier and Hippocampal Neuroinflammation in SAMP8 Mice by Inhibiting HMGB1/TLR4 and RAGE/NADPH Signaling Pathways
- 中国结合医学杂志（英文版） 2023年29卷第5期页码：448-458
- Affiliations：
  
  1.College of Acu-moxibustion and Massage, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi Province (712046), China
  2.Department of Traditional Chinese Medicine, Baotou Medical College, Baotou, Inner Mongolia Autonomous Region(014040), China
- Author bio：
  
  Dr. YANG Huan, E-mail: 102021027@btmc.edu.cn
- Funds：
  
  the National Natural Science Foundation of China(82074552);Shaanxi Science and Technology Department Project(2018JM7041);Shaanxi Province TCM "Double Chain Integration" Young and Middle-Aged Scientific Research Innovation Team Construction Project(2022-SLRH-LJ-012)
- DOI：10.1007/s11655-023-3592-5
  中图分类号：
- 纸质出版日期：2023-05，
  
  网络出版日期：2023-01-07，
  
  录用日期：2022-10-26
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Electroacupuncture Improves Blood-Brain Barrier and Hippocampal Neuroinflammation in SAMP8 Mice by Inhibiting HMGB1/TLR4 and RAGE/NADPH Signaling Pathways[J]. 中国结合医学杂志（英文版）, 2023,29(5):448-458.

WANG Yuan, WANG Qiang, LUO Di, et al. Electroacupuncture Improves Blood-Brain Barrier and Hippocampal Neuroinflammation in SAMP8 Mice by Inhibiting HMGB1/TLR4 and RAGE/NADPH Signaling Pathways[J]. Chinese Journal of Integrative Medicine, 2023,29(5):448-458.
Electroacupuncture Improves Blood-Brain Barrier and Hippocampal Neuroinflammation in SAMP8 Mice by Inhibiting HMGB1/TLR4 and RAGE/NADPH Signaling Pathways[J]. 中国结合医学杂志（英文版）, 2023,29(5):448-458. DOI： 10.1007/s11655-023-3592-5.

WANG Yuan, WANG Qiang, LUO Di, et al. Electroacupuncture Improves Blood-Brain Barrier and Hippocampal Neuroinflammation in SAMP8 Mice by Inhibiting HMGB1/TLR4 and RAGE/NADPH Signaling Pathways[J]. Chinese Journal of Integrative Medicine, 2023,29(5):448-458. DOI： 10.1007/s11655-023-3592-5.

摘要

Abstract

Objective:

To investigate the molecular mechanisms underlying the beneficial effect of electroacupuncture (EA) in experimental models of Alzheimer's disease (AD)

in vivo

Methods:

Senescence-accelerated mouse prone 8 (SAMP8) mice were used as AD models and received EA at Yingxiang (LI 20

bilateral) and Yintang (GV 29) points for 20 days. For certain experiments

SAMP8 mice were injected intravenously with human fibrin (2 mg). The Morris water maze test was used to assess cognitive and memory abilities. The changes of tight junctions of blood-brain barrier (BBB) in mice were observed by transmission electron microscope. The expressions of fibrin

amyloid-β (Aβ)

and ionized calcium-binding adapter molecule 1 (IBa-1) in mouse hippocampus (CA1/CA3) were detected by reverse transcription-quantitative polymerase chain reaction (qRT-PCR)

Western blot or immunohistochemical staining. The expression of fibrin in mouse plasma was detected by enzyme-linked immunosorbent assay. The expressions of tight junction proteins zonula occludens-1 and claudin-5 in hippocampus were detected by qRT-PCR and immunofluorescence staining. Apoptosis of hippocampal neurons was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining.

Results:

Fibrin was time-dependently deposited in the hippocampus of SAMP8 mice and this was inhibited by EA treatment (

0.05 or

0.01). Furthermore

EA treatment suppressed the accumulation of Aβ in the hippocampus of SAMP8 mice (

0.01)

which was reversed by fibrin injection (

0.05 or

0.01). EA improved SAMP8 mice cognitive impairment and BBB permeability (

0.05 or

0.01). Moreover

EA decreased reactive oxygen species levels and neuroinflammation in the hippocampus of SAMP8 mice

which was reversed by fibrin injection (

0.05 or

0.01). Mechanistically

EA inhibited the promoting effect of fibrin on the high mobility group box protein 1 (HMGB1)/toll-like receptor 4 (TLR4) and receptor for advanced glycation end products (RAGE)/nicotinamide adenine dinucleotide phosphate (NADPH) signaling pathways (

0.01).

Conclusion:

EA may potentially improve cognitive impairment in AD via inhibition of fibrin/Aβ deposition and deactivation of the HMGB1/TLR4 and RAGE/NADPH signaling pathways.

关键词

Keywords

electroacupuncturefibrin/amyloid-β depositionhigh mobility group box protein 1/toll-like receptor 4receptor for advanced glycation end products/nicotinamide adenine dinucleotide phosphateChinese medicine

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