Electroacupuncture Ameliorates Tibial Fracture-Induced Cognitive Dysfunction by Elevating 7nAChR Expression and Suppressing Mast Cell Degranulation in the Hippocampus of Rats

Overview

Journal Evid Based Complement Alternat Med

Specialty Rehabilitation Medicine

Date 2022 Apr 25

PMID 35463074

Authors

Yudi Zhou

Cheng Hu

Chenlu Mao

Sha Li

Yaomei Cui

Yanning Qian

Affiliations

Soon will be listed here.

Abstract

Intracerebral neuroinflammation, closely related to brain mast cell (MC) activation, performs an integral function in the pathogenic process of postoperative cognitive dysfunction (POCD). In addition to regulating cognitive activities, the alpha-7-nicotinic acetylcholine receptor (7nAChR) engages in the progression of cognitive deficiency. In this research, we aimed to investigate how electroacupuncture (EA) affects the cognitive function in rats after tibial fracture surgery to determine whether the underlying mechanism involves the inhibition of hippocampal MC degranulation via 7nAChR. A rat model of tibial fracture surgery for inducing POCD was developed and subjected to treatment with EA or the 7nAChR antagonist -bungarotoxin (-BGT) and the 7nAChR agonist PHA-543613. The spatial memory tasks in the Morris Water Maze (MWM) test showed that both EA and PHA-543613-treated rats performed significantly better than untreated rats, with reduced escape latency and increased frequency of passage through the platform. However, EA and PHA-543613 intervention decreased the protein and mRNA levels of High-mobility group box-1(HMGB-1) and proinflammatory cytokines tumor necrosis factor- (TNF-), interleukin-1 (IL-1) in the serum and hippocampus, respectively, by upregulating 7nAChR in the hippocampus. Furthermore, EA and PHA-543613 pretreatment reduced the number of activated MCs and suppressed neuronal apoptosis after tibial fracture surgery in the hippocampal CA1 regions, which was reversed by -BGT. The findings indicated that EA pretreatment ameliorated POCD after tibial fracture surgery in rats by inhibiting brain MC activation and neuroinflammation mediated by the 7nAChR-dependent cholinergic anti-inflammatory system.

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References

Sadigh-Eteghad S, Talebi M, Mahmoudi J, Babri S, Shanehbandi D . Selective activation of α7 nicotinic acetylcholine receptor by PHA-543613 improves Aβ25-35-mediated cognitive deficits in mice. Neuroscience. 2015; 298:81-93. DOI: 10.1016/j.neuroscience.2015.04.017. View

Zhang S, Dong H, Zhang X, Li N, Sun J, Qian Y . Cerebral mast cells contribute to postoperative cognitive dysfunction by promoting blood brain barrier disruption. Behav Brain Res. 2015; 298(Pt B):158-66. DOI: 10.1016/j.bbr.2015.11.003. View

Feng P, Deng P, Liu L, Ai Q, Yin J, Liu Z . Electroacupuncture Alleviates Postoperative Cognitive Dysfunction in Aged Rats by Inhibiting Hippocampal Neuroinflammation Activated via Microglia/TLRs Pathway. Evid Based Complement Alternat Med. 2017; 2017():6421260. PMC: 5480055. DOI: 10.1155/2017/6421260. View

Yu M, Huang H, Dong S, Sha H, Wei W, Liu C . High mobility group box-1 mediates hippocampal inflammation and contributes to cognitive deficits in high-fat high-fructose diet-induced obese rats. Brain Behav Immun. 2019; 82:167-177. DOI: 10.1016/j.bbi.2019.08.007. View

Wang Q, Wang F, Li X, Yang Q, Li X, Xu N . Electroacupuncture pretreatment attenuates cerebral ischemic injury through α7 nicotinic acetylcholine receptor-mediated inhibition of high-mobility group box 1 release in rats. J Neuroinflammation. 2012; 9:24. PMC: 3297509. DOI: 10.1186/1742-2094-9-24. View

Feng X, Degos V, Koch L, Britton S, Zhu Y, Vacas S . Surgery results in exaggerated and persistent cognitive decline in a rat model of the Metabolic Syndrome. Anesthesiology. 2013; 118(5):1098-105. PMC: 5530762. DOI: 10.1097/ALN.0b013e318286d0c9. View

Lin F, Shan W, Zheng Y, Pan L, Zuo Z . Toll-like receptor 2 activation and up-regulation by high mobility group box-1 contribute to post-operative neuroinflammation and cognitive dysfunction in mice. J Neurochem. 2021; 158(2):328-341. PMC: 8895530. DOI: 10.1111/jnc.15368. View

Qian Q, Zhang X, Wang Y, Xu J, Dong H, Li N . Pro-inflammatory role of high-mobility group box-1 on brain mast cells via the RAGE/NF-κB pathway. J Neurochem. 2019; 151(5):595-607. DOI: 10.1111/jnc.14869. View

Feng X, Uchida Y, Koch L, Britton S, Hu J, Lutrin D . Exercise Prevents Enhanced Postoperative Neuroinflammation and Cognitive Decline and Rectifies the Gut Microbiome in a Rat Model of Metabolic Syndrome. Front Immunol. 2018; 8:1768. PMC: 5732173. DOI: 10.3389/fimmu.2017.01768. View

10.

Mao C, Hu C, Zhou Y, Zou R, Li S, Cui Y . Electroacupuncture Pretreatment against Cerebral Ischemia/Reperfusion Injury through Mitophagy. Evid Based Complement Alternat Med. 2020; 2020:7486041. PMC: 7499311. DOI: 10.1155/2020/7486041. View

11.

Avelino-Silva T, Campora F, Curiati J, Jacob-Filho W . Association between delirium superimposed on dementia and mortality in hospitalized older adults: A prospective cohort study. PLoS Med. 2017; 14(3):e1002264. PMC: 5370103. DOI: 10.1371/journal.pmed.1002264. View

12.

Terrando N, Monaco C, Ma D, Foxwell B, Feldmann M, Maze M . Tumor necrosis factor-alpha triggers a cytokine cascade yielding postoperative cognitive decline. Proc Natl Acad Sci U S A. 2010; 107(47):20518-22. PMC: 2996666. DOI: 10.1073/pnas.1014557107. View

13.

Liu Q, Sun Y, Huang H, Chen C, Wan J, Ma L . Sirtuin 3 protects against anesthesia/surgery-induced cognitive decline in aged mice by suppressing hippocampal neuroinflammation. J Neuroinflammation. 2021; 18(1):41. PMC: 7863360. DOI: 10.1186/s12974-021-02089-z. View

14.

Taly A, Corringer P, Guedin D, Lestage P, Changeux J . Nicotinic receptors: allosteric transitions and therapeutic targets in the nervous system. Nat Rev Drug Discov. 2009; 8(9):733-50. DOI: 10.1038/nrd2927. View

15.

Song C, Shi J, Xu J, Zhao L, Zhang Y, Huang W . Post-transcriptional regulation of α7 nAChR expression by miR-98-5p modulates cognition and neuroinflammation in an animal model of Alzheimer's disease. FASEB J. 2021; 35(6):e21658. DOI: 10.1096/fj.202100257R. View

16.

He X, Zhao S, You W, Cai Y, Wang Y, Ye Y . Neuroprotective Effects of Electroacupuncture Preventive Treatment in Senescence-Accelerated Mouse Prone 8 Mice. Chin J Integr Med. 2016; 24(2):133-139. DOI: 10.1007/s11655-016-2265-z. View

17.

Daiello L, Racine A, Gou R, Marcantonio E, Xie Z, Kunze L . Postoperative Delirium and Postoperative Cognitive Dysfunction: Overlap and Divergence. Anesthesiology. 2019; 131(3):477-491. PMC: 6692220. DOI: 10.1097/ALN.0000000000002729. View

18.

Cao Y, Wang L, Lin L, Wang X, Ma S, Yang N . Acupuncture attenuates cognitive deficits through α7nAChR mediated anti-inflammatory pathway in chronic cerebral hypoperfusion rats. Life Sci. 2020; 266:118732. DOI: 10.1016/j.lfs.2020.118732. View

19.

Vorhees C, Williams M . Morris water maze: procedures for assessing spatial and related forms of learning and memory. Nat Protoc. 2007; 1(2):848-58. PMC: 2895266. DOI: 10.1038/nprot.2006.116. View

20.

Frasch M, Szynkaruk M, Prout A, Nygard K, Cao M, Veldhuizen R . Decreased neuroinflammation correlates to higher vagus nerve activity fluctuations in near-term ovine fetuses: a case for the afferent cholinergic anti-inflammatory pathway?. J Neuroinflammation. 2016; 13(1):103. PMC: 4894374. DOI: 10.1186/s12974-016-0567-x. View