Skip to main content
SpringerLink
Log in

Dysregulation of the Gut Microbiota Contributes to Sevoflurane-Induced Cognitive Dysfunction in Aged Mice by Activating the NLRP3 Inflammasome

  • Research
  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Postoperative cognitive dysfunction (POCD), a common complication in elderly patients after surgery, seriously affects patients’ quality of life. Long-term or repeated inhalation of sevoflurane can cause neuroinflammation, which is a risk factor for POCD. However, the underlying mechanism needs to be further explored. Recent research had revealed a correlation between neurological disorders and changes in the gut microbiota. Dysfunction of the gut microbiota is involved in the occurrence and development of central nervous system diseases. Here, we found that cognitive dysfunction in aged mice induced by sevoflurane exposure (3%, 2 hours daily, for 3 days) was related to gut microbiota dysbiosis, while probiotics improved cognitive function by alleviating dysbiosis. Sevoflurane caused a significant decrease in the abundance of Akkermansia (P<0.05), while probiotics restored the abundance of Akkermansia. Compared to those in the control group, sevoflurane significantly increased the expression of NLRP3 inflammasome-associated proteins in the gut and brain in the sevoflurane-exposed group, thus causing neuroinflammation and synaptic damage, which probiotics can mitigate (con vs. sev, P < 0.01; p+sev vs. sev, P < 0.05). In conclusion, for the first time, our study revealed that dysbiosis of the gut microbiota caused by sevoflurane anesthesia contributes to the NLRP3 inflammasome-mediated neuroinflammation and cognitive dysfunction from the perspective of the gut-brain axis. Perhaps postoperative cognitive impairment in elderly patients can be alleviated or even prevented by regulating the gut microbiota. This study provides new insights and methods for the prevention and treatment of cognitive impairment induced by sevoflurane.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Data Availability

All data supporting the findings of this study are available to the corresponding author upon request.

References

  1. Kotekar N, Shenkar A, Nagaraj R (2018) Postoperative cognitive dysfunction - current preventive strategies. Clin Interv Aging 13:2267–2273. https://doi.org/10.2147/CIA.S133896

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Evered LA, Silbert BS (2018) Postoperative Cognitive Dysfunction and Noncardiac Surgery. Anesth Analg 127(2):496–505. https://doi.org/10.1213/ANE.0000000000003514

    Article  PubMed  Google Scholar 

  3. Moller JT, Cluitmans P, Rasmussen LS, Houx P, Rasmussen H, Canet J, Rabbitt P, Jolles J et al (1998) Long-term postoperative cognitive dysfunction in the elderly ISPOCD1 study. ISPOCD investigators. International Study of Post-Operative Cognitive Dysfunction. Lancet (London, England) 351(9106):857–861. https://doi.org/10.1016/s0140-6736(97)07382-0

    Article  CAS  PubMed  Google Scholar 

  4. Rohan D, Buggy DJ, Crowley S, Ling FK, Gallagher H, Regan C, Moriarty DC (2005) Increased incidence of postoperative cognitive dysfunction 24 hr after minor surgery in the elderly. Can J Anesth 52(2):137–142. https://doi.org/10.1007/BF03027718

    Article  PubMed  Google Scholar 

  5. Qiao Y, Feng H, Zhao T, Yan H, Zhang H, Zhao X (2015) Postoperative cognitive dysfunction after inhalational anesthesia in elderly patients undergoing major surgery: the influence of anesthetic technique, cerebral injury and systemic inflammation. BMC Anesthesiol 15:154. https://doi.org/10.1186/s12871-015-0130-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Xu Y, Wang X, Xu Z, Sun F, Tian Y (2023) Tbx2 knockdown alleviated sevoflurane-induced cognitive disorder and neuron damages in aged rats via suppressing oxidative stress and ferroptosis. Toxicol Sci 195(2):257–269. https://doi.org/10.1093/toxsci/kfad071

    Article  CAS  PubMed  Google Scholar 

  7. Liu L, Liu C, Fang L (2021) AMPK-SIRT1 pathway dysfunction contributes to neuron apoptosis and cognitive impairment induced by sevoflurane. Mol Med Rep 23(1):56. https://doi.org/10.3892/mmr.2020.11694

    Article  CAS  PubMed  Google Scholar 

  8. Golomb SM, Guldner IH, Zhao A, Wang Q, Palakurthi B, Aleksandrovic EA, Lopez JA, Lee SW et al (2020) Multi-modal Single-Cell Analysis Reveals Brain Immune Landscape Plasticity during Aging and Gut Microbiota Dysbiosis. Cell Rep 33(9):108438. https://doi.org/10.1016/j.celrep.2020.108438

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Parker A, Fonseca S, Carding SR (2020) Gut microbes and metabolites as modulators of blood-brain barrier integrity and brain health. Gut Microbes 11(2):135–157. https://doi.org/10.1080/19490976.2019.1638722

    Article  CAS  PubMed  Google Scholar 

  10. Selkrig J, Wong P, Zhang X, Pettersson S (2014) Metabolic tinkering by the gut microbiome: Implications for brain development and function. Gut Microbes 5(3):369–380. https://doi.org/10.4161/gmic.28681

    Article  PubMed  PubMed Central  Google Scholar 

  11. Bonfili L, Cecarini V, Berardi S, Scarpona S, Suchodolski JS, Nasuti C, Fiorini D, Boarelli MC et al (2017) Microbiota modulation counteracts Alzheimer's disease progression influencing neuronal proteolysis and gut hormones plasma levels. Sci Rep 7(1):2426. https://doi.org/10.1038/s41598-017-02587-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Zhao X, Kong M, Wang Y, Mao Y, Xu H, He W, He Y, Gu J (2023) Nicotinamide mononucleotide improves the Alzheimer's disease by regulating intestinal microbiota. Biochem Biophys Res Commun 670:27–35. https://doi.org/10.1016/j.bbrc.2023.05.075

    Article  CAS  PubMed  Google Scholar 

  13. Liu Z, Dai X, Zhang H, Shi R, Hui Y, Jin X, Zhang W, Wang L et al (2020) Gut microbiota mediates intermittent-fasting alleviation of diabetes-induced cognitive impairment. Nat Commun 11(1):855. https://doi.org/10.1038/s41467-020-14676-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Liu J, Sun J, Wang F, Yu X, Ling Z, Li H, Zhang H, Jin J et al (2015) Neuroprotective Effects of Clostridium butyricum against Vascular Dementia in Mice via Metabolic Butyrate. Biomed Res Int 2015:412946. https://doi.org/10.1155/2015/412946

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Sun Y, Baptista LC, Roberts LM, Jumbo-Lucioni P, McMahon LL, Buford TW, Carter CS (2020) The Gut Microbiome as a Therapeutic Target for Cognitive Impairment. J Gerontol A Biol Sci Med Sci 75(7):1242–1250. https://doi.org/10.1093/gerona/glz281

    Article  CAS  PubMed  Google Scholar 

  16. Han C, Zhang Z, Guo N, Li X, Yang M, Peng Y, Ma X, Yu K et al (2021) Effects of Sevoflurane Inhalation Anesthesia on the Intestinal Microbiome in Mice. Front Cell Infect Microbiol 11:633527. https://doi.org/10.3389/fcimb.2021.633527

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Cui RS, Wang K, Wang ZL (2018) Sevoflurane anesthesia alters cognitive function by activating inflammation and cell death in rats. Exp Ther Med 15(5):4127–4130. https://doi.org/10.3892/etm.2018.5976

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. de Carvalho Ribeiro M, Szabo G (2022) Role of the Inflammasome in Liver Disease. Annu Rev Pathol 17:345–365. https://doi.org/10.1146/annurev-pathmechdis-032521-102529

    Article  CAS  PubMed  Google Scholar 

  19. Mangan MSJ, Olhava EJ, Roush WR, Seidel HM, Glick GD, Latz E (2018) Targeting the NLRP3 inflammasome in inflammatory diseases. Nat Rev Drug Discov 17(9):688. https://doi.org/10.1038/nrd.2018.149

    Article  CAS  PubMed  Google Scholar 

  20. Zhou K, Shi L, Wang Y, Chen S, Zhang J (2016) Recent Advances of the NLRP3 Inflammasome in Central Nervous System Disorders. J Immunol Res 2016:9238290. https://doi.org/10.1155/2016/9238290

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Yao H, Zhang D, Yu H, Yuan H, Shen H, Lan X, Liu H, Chen X et al (2023) Gut microbiota regulates chronic ethanol exposure-induced depressive-like behavior through hippocampal NLRP3-mediated neuroinflammation. Mol Psychiatry 28(2):919–930. https://doi.org/10.1038/s41380-022-01841-y

    Article  CAS  PubMed  Google Scholar 

  22. Kim CS, Cha L, Sim M, Jung S, Chun WY, Baik HW, Shin DM (2021) Probiotic Supplementation Improves Cognitive Function and Mood with Changes in Gut Microbiota in Community-Dwelling Older Adults: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial. J Gerontol A Biol Sci Med Sci 76(1):32–40. https://doi.org/10.1093/gerona/glaa090

    Article  CAS  PubMed  Google Scholar 

  23. Chapman TM, Plosker GL, Figgitt DP (2006) VSL#3 probiotic mixture: a review of its use in chronic inflammatory bowel diseases. Drugs 66(10):1371–1387. https://doi.org/10.2165/00003495-200666100-00006

    Article  CAS  PubMed  Google Scholar 

  24. Chen X, Fu Y, Wang L, Qian W, Zheng F, Hou X (2019) Bifidobacterium longum and VSL#3® amelioration of TNBS-induced colitis associated with reduced HMGB1 and epithelial barrier impairment. Dev Comp Immunol 92:77–86. https://doi.org/10.1016/j.dci.2018.09.006

    Article  CAS  PubMed  Google Scholar 

  25. Han D, Li Z, Liu T, Yang N, Li Y, He J, Qian M, Kuang Z et al (2020) Prebiotics Regulation of Intestinal Microbiota Attenuates Cognitive Dysfunction Induced by Surgery Stimulation in APP/PS1 Mice. Aging Dis 11(5):1029–1045. https://doi.org/10.14336/AD.2020.0106

    Article  PubMed  PubMed Central  Google Scholar 

  26. Yu Y, Yang Y, Tan H, Boukhali M, Khatri A, Yu Y, Hua F, Liu L et al (2020) Tau Contributes to Sevoflurane-induced Neurocognitive Impairment in Neonatal Mice. Anesthesiology 133(3):595–610. https://doi.org/10.1097/ALN.0000000000003452

    Article  CAS  PubMed  Google Scholar 

  27. Shen X, Dong Y, Xu Z, Wang H, Miao C, Soriano SG, Sun D, Baxter MG et al (2013) Selective anesthesia-induced neuroinflammation in developing mouse brain and cognitive impairment. Anesthesiology 118(3):502–515. https://doi.org/10.1097/ALN.0b013e3182834d77

    Article  CAS  PubMed  Google Scholar 

  28. Mariman R, Tielen F, Koning F, Nagelkerken L (2015) The Probiotic Mixture VSL#3 Has Differential Effects on Intestinal Immune Parameters in Healthy Female BALB/c and C57BL/6 Mice. J Nutr 145(6):1354–1361. https://doi.org/10.3945/jn.114.199729

    Article  CAS  PubMed  Google Scholar 

  29. Bevins RA, Besheer J (2006) Object recognition in rats and mice: a one-trial non-matching-to-sample learning task to study ‘recognition memory’. Nat Protoc 1(3):1306–1311. https://doi.org/10.1038/nprot.2006.205

    Article  PubMed  Google Scholar 

  30. Yang D, Wang Z, Chen Y, Guo Q, Dong Y (2023) Interactions between gut microbes and NLRP3 inflammasome in the gut-brain axis. Comput Struct Biotechnol J 21:2215–2227. https://doi.org/10.1016/j.csbj.2023.03.017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Zhao L, Gong H, Huang H, Tuerhong G, Xia H (2021) Participation of Mind Bomb-2 in Sevoflurane Anesthesia Induces Cognitive Impairment in Aged Mice via Modulating Ferroptosis. ACS Chem Neurosci 12(13):2399–2408. https://doi.org/10.1021/acschemneuro.1c00131

    Article  CAS  PubMed  Google Scholar 

  32. Sampson TR, Debelius JW, Thron T, Janssen S, Shastri GG, Ilhan ZE, Challis C, Schretter CE et al (2016) Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson’s Disease. Cell 167(6):1469–1480.e12. https://doi.org/10.1016/j.cell.2016.11.018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Kowalski K, Mulak A (2019) Brain-Gut-Microbiota Axis in Alzheimer's Disease. J Neurogastroenterol Motil 25(1):48–60. https://doi.org/10.5056/jnm18087

    Article  PubMed  PubMed Central  Google Scholar 

  34. Png CW, Lindén SK, Gilshenan KS, Zoetendal EG, McSweeney CS, Sly LI, McGuckin MA, Florin TH (2010) Mucolytic bacteria with increased prevalence in IBD mucosa augment in vitro utilization of mucin by other bacteria. Am J Gastroenterol 105(11):2420–2428. https://doi.org/10.1038/ajg.2010.281

    Article  CAS  PubMed  Google Scholar 

  35. Harach T, Marungruang N, Duthilleul N, Cheatham V, Mc Coy KD, Frisoni G, Neher JJ, Fåk F et al (2017) Reduction of Abeta amyloid pathology in APPPS1 transgenic mice in the absence of gut microbiota. Sci Rep 7:41802. https://doi.org/10.1038/srep41802

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Ou Z, Deng L, Lu Z, Wu F, Liu W, Huang D, Peng Y (2020) Protective effects of Akkermansia muciniphila on cognitive deficits and amyloid pathology in a mouse model of Alzheimer's disease. Nutr Diabetes 10(1):12. https://doi.org/10.1038/s41387-020-0115-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Li N, Tan S, Wang Y, Deng J, Wang N, Zhu S, Tian W, Xu J et al (2023) Akkermansia muciniphila supplementation prevents cognitive impairment in sleep-deprived mice by modulating microglial engulfment of synapses. Gut Microbes 15(2):2252764. https://doi.org/10.1080/19490976.2023.2252764

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Lamkanfi M, Dixit VM (2014) Mechanisms and functions of inflammasome. Cell 157(5):1013–1022. https://doi.org/10.1016/j.cell.2014.04.007

    Article  CAS  PubMed  Google Scholar 

  39. Kelley N, Jeltema D, Duan Y, He Y (2019) The NLRP3 Inflammasome: An Overview of Mechanisms of Activation and Regulation. Int J Mol Sci 20(13):3328. https://doi.org/10.3390/ijms20133328

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Neudecker V, Haneklaus M, Jensen O, Khailova L, Masterson JC, Tye H, Biette K, Jedlicka P et al (2017) Myeloid-derived miR-223 regulates intestinal inflammation via repression of the NLRP3 inflammasome. J Exp Med 214(6):1737–1752. https://doi.org/10.1084/jem.20160462

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Zaki MH, Boyd KL, Vogel P, Kastan MB, Lamkanfi M, Kanneganti TD (2010) The NLRP3 inflammasome protects against loss of epithelial integrity and mortality during experimental colitis. Immunity 32(3):379–391. https://doi.org/10.1016/j.immuni.2010.03.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Seo SU, Kamada N, Muñoz-Planillo R, Kim YG, Kim D, Koizumi Y, Hasegawa M, Himpsl SD et al (2015) Distinct Commensals Induce Interleukin-1β via NLRP3 Inflammasome in Inflammatory Monocytes to Promote Intestinal Inflammation in Response to Injury. Immunity 42(4):744–755. https://doi.org/10.1016/j.immuni.2015.03.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Mai CT, Wu MM, Wang CL, Su ZR, Cheng YY, Zhang XJ (2019) Palmatine attenuated dextran sulfate sodium (DSS)-induced colitis via promoting mitophagy-mediated NLRP3 inflammasome inactivation. Mol Immunol 105:76–85. https://doi.org/10.1016/j.molimm.2018.10.015

    Article  CAS  PubMed  Google Scholar 

  44. Pellegrini C, Antonioli L, Calderone V, Colucci R, Fornai M, Blandizzi C (2020) Microbiota-gut-brain axis in health and disease: Is NLRP3 inflammasome at the crossroads of microbiota-gut-brain communications? Prog Neurobiol 191:101806. https://doi.org/10.1016/j.pneurobio.2020.101806

    Article  CAS  PubMed  Google Scholar 

  45. Wu AG, Zhou XG, Qiao G, Yu L, Tang Y, Yan L, Qiu WQ, Pan R et al (2021) Targeting microglial autophagic degradation in NLRP3 inflammasome-mediated neurodegenerative diseases. Ageing Res Rev 65:101202. https://doi.org/10.1016/j.arr.2020.101202

    Article  CAS  PubMed  Google Scholar 

  46. Shukla PK, Delotterie DF, Xiao J, Pierre JF, Rao R, McDonald MP, Khan MM (2021) Alterations in the Gut-Microbial-Inflammasome-Brain Axis in a Mouse Model of Alzheimer's Disease. Cells 10(4):779. https://doi.org/10.3390/cells10040779

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Shen H, Guan Q, Zhang X, Yuan C, Tan Z, Zhai L, Hao Y, Gu Y et al (2020) New mechanism of neuroinflammation in Alzheimer's disease: The activation of NLRP3 inflammasome mediated by gut microbiota. Prog Neuro-Psychopharmacol Biol Psychiatry 100:109884. https://doi.org/10.1016/j.pnpbp.2020.109884

    Article  CAS  Google Scholar 

  48. Lowe PP, Gyongyosi B, Satishchandran A, Iracheta-Vellve A, Cho Y, Ambade A, Szabo G (2018) Reduced gut microbiome protects from alcohol-induced neuroinflammation and alters intestinal and brain inflammasome expression. J Neuroinflammation 15(1):298. https://doi.org/10.1186/s12974-018-1328-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Kutlu MG, Gould TJ (2016) Effects of drugs of abuse on hippocampal plasticity and hippocampus-dependent learning and memory: contributions to development and maintenance of addiction. Learn Mem (Cold Spring Harbor, NY) 23(10):515–533. https://doi.org/10.1101/lm.042192.116

    Article  CAS  Google Scholar 

  50. Gustin A, Kirchmeyer M, Koncina E, Felten P, Losciuto S, Heurtaux T, Tardivel A, Heuschling P et al (2015) NLRP3 Inflammasome Is Expressed and Functional in Mouse Brain Microglia but Not in Astrocytes. PLoS One 10(6):e0130624. https://doi.org/10.1371/journal.pone.0130624

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Luo Y, Reis C, Chen S (2019) NLRP3 Inflammasome in the Pathophysiology of Hemorrhagic Stroke: A Review. Curr Neuropharmacol 17(7):582–589. https://doi.org/10.2174/1570159X17666181227170053

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Borre YE, O'Keeffe GW, Clarke G, Stanton C, Dinan TG, Cryan JF (2014) Microbiota and neurodevelopmental windows: implications for brain disorders. Trends Mol Med 20(9):509–518. https://doi.org/10.1016/j.molmed.2014.05.002

    Article  PubMed  Google Scholar 

  53. Zhao L, Zhang C, Cao G, Dong X, Li D, Jiang L (2019) Higher Circulating Trimethylamine N-oxide Sensitizes Sevoflurane-Induced Cognitive Dysfunction in Aged Rats Probably by Downregulating Hippocampal Methionine Sulfoxide Reductase A. Neurochem Res 44(11):2506–2516. https://doi.org/10.1007/s11064-019-02868-4

    Article  CAS  PubMed  Google Scholar 

  54. Neves G, Cooke SF, Bliss TV (2008) Synaptic plasticity, memory and the hippocampus: a neural network approach to causality. Nat Rev Neurosci 9(1):65–75. https://doi.org/10.1038/nrn2303

    Article  CAS  PubMed  Google Scholar 

  55. Jones RS, Lynch MA (2015) How dependent is synaptic plasticity on microglial phenotype? Neuropharmacology 96(Pt A):3–10. https://doi.org/10.1016/j.neuropharm.2014.08.012

    Article  CAS  PubMed  Google Scholar 

  56. Shao A, Fei J, Feng S, Weng J (2020) Chikusetsu saponin IVa alleviated sevoflurane-induced neuroinflammation and cognitive impairment by blocking NLRP3/caspase-1 pathway. Pharmacol Rep 72(4):833–845. https://doi.org/10.1007/s43440-020-00078-2

    Article  CAS  PubMed  Google Scholar 

  57. McNabney SM, Henagan TM (2017) Short Chain Fatty Acids in the Colon and Peripheral Tissues: A Focus on Butyrate, Colon Cancer, Obesity and Insulin Resistance. Nutrients 9(12):1348. https://doi.org/10.3390/nu9121348

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Geirnaert A, Steyaert A, Eeckhaut V, Debruyne B, Arends JB, Van Immerseel F, Boon N, Van de Wiele T (2014) Butyricicoccus pullicaecorum, a butyrate producer with probiotic potential, is intrinsically tolerant to stomach and small intestine conditions. Anaerobe 30:70–74. https://doi.org/10.1016/j.anaerobe.2014.08.010

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by grants from the Key Project of Jiangsu Province Elderly Health Research Project (grant number: LKZ2023015) and the Major Scientific Research Project of Wuxi Health Commission, Jiangsu Province (grant number: Z202211).

Institutional Review Board Statement

The experimental plan was approved by the Animal Ethics Committee of Jiangnan University (ethics number: JN.No20221030c0800530[453]).

Funding

This research was funded by the Key Project of Jiangsu Province Elderly Health Research Project (grant number: LKZ2023015) and the Major Scientific Research Project of Wuxi Health Commission, Jiangsu Province (grant number: Z202211).

Author information

Authors and Affiliations

  1. Department of Anesthesiology, Wuxi Maternal and Child Health Care Hospital Affiliated to Jiangnan University, Wuxi, 214002, China

    Shanshan Han & Dengxin Zhang

  2. Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, China

    Shanshan Han, Ruxi Bian, Yuxuan Chen, Junjie Liang & Peng Zhao

  3. Department of Gynecology, Jiangnan University Affiliated Hospital, Wuxi, 214002, China

    Yanfang Gu

Authors
  1. Shanshan Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ruxi Bian
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yuxuan Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Junjie Liang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Peng Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yanfang Gu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Dengxin Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceptualization, Shanshan Han; methodology, Shanshan Han and Ruxi Bian; software, Shanshan Han; validation, Shanshan Han, Ruxi Bian and Yuxuan Chen; formal analysis, Shanshan Han and Ruxi Bian; investigation, Shanshan Han, Yuxuan Chen and Junjie Liang; resources, Dengxin Zhang; data curation, Ruxi Bian and Junjie Liang; writing—original draft preparation, Shanshan Han; writing—review and editing, Dengxin Zhang and Yanfang Gu; visualization, Ruxi Bian and Yuxuan Chen; supervision Yanfang Gu and Peng Zhao; project administration, Dengxin Zhang and Yanfang Gu; funding acquisition, Dengxin Zhang. All authors have read and agreed to the published version of the manuscript.

Corresponding authors

Correspondence to Yanfang Gu or Dengxin Zhang.

Ethics declarations

Ethics Approval

This study was approved by the Animal Ethics Committee of Jiangnan University (Date: JN.No20221030c0800530[453]).

Consent to Participate

Not applicable.

Consent for Publication

Not applicable.

Informed Consent

Not applicable.

Conflict of Interest

The authors declare no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Han, S., Bian, R., Chen, Y. et al. Dysregulation of the Gut Microbiota Contributes to Sevoflurane-Induced Cognitive Dysfunction in Aged Mice by Activating the NLRP3 Inflammasome. Mol Neurobiol (2024). https://doi.org/10.1007/s12035-024-04229-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12035-024-04229-x

Keywords

Search

Navigation