Article Menu

Export Article

More by Authors Links

Article Data

  • Views 1218
  • Dowloads 130

Original Research

Open Access

HOMER1A restores sevoflurane-induced cognitive dysfunction by regulating microglia's activation through activating the AMPK/TXNIP axis

  • Guangzhen Zhao1
  • Jianmin Jing2,*,

1Department of Neurology, Beijing Longfu Hospital, 100010 Beijing, China

2Department of Anesthesia, ShanXi Provincial People’s Hospital, 030012 Taiyuan, Shanxi, China

DOI: 10.22514/sv.2023.065 Vol.19,Issue 4,July 2023 pp.202-212

Submitted: 28 April 2023 Accepted: 12 June 2023

Published: 08 July 2023

*Corresponding Author(s): Jianmin Jing E-mail: jingjianmin_dr66@163.com

PDF (4.38 MB) Supplementary material View Full-text

Abstract

More and more researchers have discovered that the employment of anesthetics can lead to cognitive dysfunction of brain. HOMER1A has been investigated to have neuroprotective effects. Sevoflurane (SEV) is the most common inhaled anesthetic utilized in surgery, but the role of HOMER1A in SEV-induced cognitive dysfunction is unclear. Thus, in this study, SEV was utilized in our study for investigating the role of HOMER1A. At first, the rat model was established through inhaling 2% SEV. Results from our study uncovered that the brain tissues of SEV-treated rats were severely damaged, and the levels of S-100β and neuron-specific enolase (NSE) were markedly elevated after SEV treatment. Further study showed that HOMER1A exhibited lower expression in the brain tissues of SEV-mediated rats. In addition, HOMER1A ameliorated nerve injury and cognitive deficit in SEV-treated rats. Moreover, HOMER1A improved inflammation in the brain tissues of SEV-induced rats. HOMER1A suppressed SEV-stimulated microglial activation through modulating M1/M2 polarization. Besides, HOMER1A activated Adenosine 5’-monophosphate (AMP)-activated protein kinase (AMPK) pathway to reduce thioredoxin interacting protein (TXNIP) expression. Finally, through rescue assays, inhibition of AMPK activation (Compound C (CC) treatment) attenuated the neuroprotective effects of HOMER1A in SEV-triggered rats. In summary, HOMER1A regulated microglia M1/M2 polarization to restore SEV-stimulated cognitive dysfunction through activating the AMPK/TXNIP axis.


Keywords

HOMER1A; Sevoflurane; Cognitive dysfunction; M1/M2 polarization; AMPK/TXNIP axis


Cite and Share

Guangzhen Zhao,Jianmin Jing. HOMER1A restores sevoflurane-induced cognitive dysfunction by regulating microglia's activation through activating the AMPK/TXNIP axis. Signa Vitae. 2023. 19(4);202-212.

URL:

https://www.signavitae.com/articles/10.22514/sv.2023.065

References

[1] Wang CM, Chen WC, Zhang Y, Lin S, He HF. Update on the mechanism and treatment of sevoflurane-induced postoperative cognitive dysfunction. Frontiers in Aging Neuroscience. 2021; 13: 702231.

[2] Liu J, Huang K, Zhu B, Zhou B, Ahmad Harb AK, Liu L, et al. Neuropsychological tests in post-operative cognitive dysfunction: methods and applications. Frontiers in Psychology. 2021; 12: 684307.

[3] Yu H, Kang H, Fan J, Cao G, Liu B. Influence of dexmedetomidine on postoperative cognitive dysfunction in the elderly: a meta-analysis of randomized controlled trials. Brain and Behavior. 2022; 12: e2665.

[4] Palanca BJA, Avidan MS, Mashour GA. Human neural correlates of sevoflurane-induced unconsciousness. British Journal of Anaesthesia. 2017; 119: 573–582.

[5] Sun M, Xie Z, Zhang J, Leng Y. Mechanistic insight into sevoflurane-associated developmental neurotoxicity. Cell Biology and Toxicology. 2022; 38: 927–943.

[6] Yang X, Zhang W, Wu H, Fu S, Yang J, Liu S, et al. Downregulation of CDK5 restores sevoflurane-induced cognitive dysfunction by promoting SIRT1-mediated autophagy. Cellular and Molecular Neurobiology. 2020; 40: 955–965.

[7] Wei W, Sun Z, He S, Zhang W, Chen S. Protective role of dexmedetomi-dine against sevoflurane-induced postoperative cognitive dysfunction via the microRNA-129/TLR4 axis. Journal of Clinical Neuroscience. 2021; 92: 89–97.

[8] Yu Y, Zhang W, Zhu D, Wang H, Shao H, Zhang Y. LncRNA Rian ameliorates sevoflurane anesthesia-induced cognitive dysfunction through regulation of miR-143-3p/LIMK1 axis. Human Cell. 2021; 34: 808–818.

[9] He B, Wang J. METTL3 regulates hippocampal gene transcription via N6-methyladenosine methylation in sevoflurane-induced postoperative cognitive dysfunction mouse. Aging. 2021; 13: 23108–23118.

[10] Ahmad Hariza AM, Mohd Yunus MH, Murthy JK, Wahab S. Clinical improvement in depression and cognitive deficit following electroconvulsive therapy. Diagnostics. 2023; 13: 1585.

[11] Reshetnikov VV, Bondar NP. The role of stress-induced changes of Homer1 expression in stress susceptibility. Biochemistry. 2021; 86: 613–626.

[12] Wang Y, Zhao M, Shang L, Zhang Y, Huang C, He Z, et al. Homer1a protects against neuronal injury via PI3K/AKT/mTOR signaling pathway. International Journal of Neuroscience. 2020; 130: 621–630.

[13] Fei F, Li J, Rao W, Liu W, Chen X, Su N, et al. Upregulation of Homer1a promoted retinal ganglion cell survival after retinal ischemia and reperfusion via interacting with Erk pathway. Cellular and Molecular Neurobiology. 2015; 35: 1039–1048.

[14] Serchov T, Schwarz I, Theiss A, Sun L, Holz A, Döbrössy MD, et al. Enhanced adenosine A1 receptor and Homer1a expression in hippocampus modulates the resilience to stress-induced depression-like behavior. Neuropharmacology. 2020; 162: 107834.

[15] Tappe A, Klugmann M, Luo C, Hirlinger D, Agarwal N, Benrath J, et al. Synaptic scaffolding protein Homer1a protects against chronic inflammatory pain. Nature Medicine. 2006; 12: 677–681.

[16] Orihuela R, McPherson CA, Harry GJ. Microglial M1/M2 polarization and metabolic states. British Journal of Pharmacology. 2016; 173: 649–665.

[17] Iadecola C, Anrather J. The immunology of stroke: from mechanisms to translation. Nature Medicine. 2011; 17: 796–808.

[18] Shan W, Nagai T, Tanaka M, Itoh N, Furukawa-Hibi Y, Nabeshima T, et al. Neuronal PAS domain protein 4 (Npas4) controls neuronal homeostasis in pentylenetetrazole-induced epilepsy through the induction of Homer1a. Journal of Neurochemistry. 2018; 145: 19–33.

[19] Li GF, Li ZB, Zhuang SJ, Li GC. Inhibition of microRNA-34a protects against propofol anesthesia-induced neurotoxicity and cognitive dysfunction via the MAPK/ERK signaling pathway. Neuroscience Letters. 2018; 675: 152–159.

[20] Zhou X, Zhang C, Wang L, Jin S. Remimazolam induced cognitive dysfunction in mice via glutamate excitotoxicity. Translational Neuro-science. 2022; 13: 104–115.

[21] Zheng S, Shi B, Li X, Yuan H, Feng Y. Cucurbitacin E reduces the cognitive dysfunction induced by sevoflurane in rats by regulating NF-κB pathway. Acta Biochimica Polonica. 2022; 69: 387–391.

[22] Zhang Q, Li Y, Yu J, Yin C, Guo J, Zhao J, et al. TLR3 deletion inhibits programmed necrosis of brain cells in neonatal mice with sevoflurane-induced cognitive dysfunction. Aging. 2022; 14: 4714–4727.

[23] Fei Z, Fei F, Wu X, Su N. Homer signaling pathways as effective therapeutic targets for ischemic and traumatic brain injuries and retinal lesions. Neural Regeneration Research. 2022; 17: 1454.

[24] Guo S, Wang H, Yin Y. Microglia polarization from M1 to M2 in neurodegenerative diseases. Frontiers in Aging Neuroscience. 2022; 14: 815347.

[25] Lukens JR, Eyo UB. Microglia and neurodevelopmental disorders. Annual Review of Neuroscience. 2022; 45: 425–445.

[26] Xu L, He D, Bai Y. Microglia-mediated inflammation and neurodegen-erative disease. Molecular Neurobiology. 2016; 53: 6709–6715.

[27] Jiang T, Xu S, Shen Y, Xu Y, Li Y. Genistein attenuates isoflurane-induced neuroinflammation by Inhibiting TLR4-mediated microglial-polarization in vivo and in vitro. Journal of Inflammation Research. 2021; 14: 2587–2600.

[28] Yu J, Wang W, Matei N, Li X, Pang J, Mo J, et al. Ezetimibe attenuates oxidative stress and neuroinflammation via the AMPK/Nrf2/TXNIP pathway after MCAO in rats. Oxidative Medicine and Cellular Longevity. 2020; 2020: 1–14.

[29] Yang LH, Xu YC, Zhang W. Neuroprotective effect of CTRP3 over-expression against sevoflurane anesthesia-induced cognitive dysfunction in aged rats through activating AMPK/SIRT1 and PI3K/AKT signaling pathways. European Review for Medical and Pharmacological Sciences. 2020; 24: 5091–5100.

[30] Liu L, Liu C, Fang L. AMPK‑SIRT1 pathway dysfunction contributes to neuron apoptosis and cognitive impairment induced by sevoflurane. Molecular Medicine Reports. 2021; 23: 56.

[31] Yan W, Wang D, Ren D, Wang L, Hu Z, Ma Y, et al. AMPKα1 overexpression improves postoperative cognitive dysfunction in aged rats through AMPK-Sirt1 and autophagy signaling. Journal of Cellular Biochemistry. 2019; 120: 11633–11641.

[32] Wu X, Luo P, Rao W, Dai S, Zhang L, Ma W, et al. Homer1a attenuates hydrogen peroxide-induced oxidative damage in HT-22 cells through AMPK-dependent autophagy. Frontiers in Neuroscience. 2018; 12: 51.


Abstracted / indexed in

Science Citation Index Expanded (SciSearch) Created as SCI in 1964, Science Citation Index Expanded now indexes over 9,200 of the world’s most impactful journals across 178 scientific disciplines. More than 53 million records and 1.18 billion cited references date back from 1900 to present.

Journal Citation Reports/Science Edition Journal Citation Reports/Science Edition aims to evaluate a journal’s value from multiple perspectives including the journal impact factor, descriptive data about a journal’s open access content as well as contributing authors, and provide readers a transparent and publisher-neutral data & statistics information about the journal.

Chemical Abstracts Service Source Index The CAS Source Index (CASSI) Search Tool is an online resource that can quickly identify or confirm journal titles and abbreviations for publications indexed by CAS since 1907, including serial and non-serial scientific and technical publications.

Index Copernicus The Index Copernicus International (ICI) Journals database’s is an international indexation database of scientific journals. It covered international scientific journals which divided into general information, contents of individual issues, detailed bibliography (references) sections for every publication, as well as full texts of publications in the form of attached files (optional). For now, there are more than 58,000 scientific journals registered at ICI.

Geneva Foundation for Medical Education and Research The Geneva Foundation for Medical Education and Research (GFMER) is a non-profit organization established in 2002 and it works in close collaboration with the World Health Organization (WHO). The overall objectives of the Foundation are to promote and develop health education and research programs.

Scopus: CiteScore 1.0 (2022) Scopus is Elsevier's abstract and citation database launched in 2004. Scopus covers nearly 36,377 titles (22,794 active titles and 13,583 Inactive titles) from approximately 11,678 publishers, of which 34,346 are peer-reviewed journals in top-level subject fields: life sciences, social sciences, physical sciences and health sciences.

Embase Embase (often styled EMBASE for Excerpta Medica dataBASE), produced by Elsevier, is a biomedical and pharmacological database of published literature designed to support information managers and pharmacovigilance in complying with the regulatory requirements of a licensed drug.

Submission Turnaround Time

Conferences

Top