Clostridium butyricum improves cognitive dysfunction in ICV-STZ-induced Alzheimer's disease mice via suppressing TLR4 signaling pathway through the gut-brain axis.

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  • Additional Information
    • Source:
      Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
    • Publication Information:
      Original Publication: San Francisco, CA : Public Library of Science
    • Subject Terms:
      Alzheimer Disease*/pathology ; Clostridium butyricum*/metabolism ; Cognitive Dysfunction*/chemically induced; Mice ; Animals ; tau Proteins/metabolism ; Toll-Like Receptor 4/genetics ; Toll-Like Receptor 4/metabolism ; NF-kappa B/metabolism ; Brain-Gut Axis ; Streptozocin/pharmacology ; Myeloid Differentiation Factor 88/genetics ; Myeloid Differentiation Factor 88/metabolism ; Occludin/genetics ; Occludin/metabolism ; RNA, Ribosomal, 16S ; Disease Models, Animal ; Signal Transduction
    • Abstract:
      In recent years, the relationship between gut-brain axis and Alzheimer's disease (AD) attracted increasing attention. The aim of this study is to investigate the therapeutic effect of Clostridium butyricum (CB) on intraventricular injection of streptozotocin (ICV-STZ)-induced mice and the potential mechanisms. ICV-STZ mice were treated with CB by gavage for 21 consecutive days. The pharmacological effect of CB was assessed by behavior test, brain tissue H&E staining and tau protein phosphorylation levels of hippocampus tissues. The expression levels of TLR4, MYD88, NF-κB p65, TNF-α, iNOS, Occludin and ZO-1 in hippocampal and colonic tissues were detected by Western-blot method. 16S rRNA gene sequencing analysis was used to analyze the intestinal microbiota of mice. The results showed that CB improved the cognitive dysfunction of ICV-STZ mice, restored the structure and cell number of hippocampal and cortical neurons, decreased the protein levels of pSer404-tau protein in hippocampal tissues and TLR4, MYD88, NF-κB p65 and iNOS in hippocampal and colonic tissues, and increased the protein levels of Occludin and ZO-1 in colonic tissues. Meanwhile, CB reversed the changes of intestinal microbiota in AD mice. Therefore, the mechanisms of cognitive function and brain pathological changes in AD mice improved by CB may be related to the regulation of TLR4 signaling pathway and intestinal microbiota. This study supports the potential anti-AD effect of CB and initially revealed its pharmacological mechanism of CB, providing a theoretical basis for further clinical application of CB.
      Competing Interests: The authors have declared that no competing interests exist.
      (Copyright: © 2023 Su et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
    • References:
      Alzheimers Dement (N Y). 2020 Jul 16;6(1):e12050. (PMID: 32695874)
      Brain. 2020 Sep 1;143(9):2803-2817. (PMID: 32812023)
      Alzheimers Dement. 2018 Apr;14(4):483-491. (PMID: 29433981)
      Nat Neurosci. 2018 Oct;21(10):1359-1369. (PMID: 30258234)
      Front Immunol. 2021 May 31;12:683068. (PMID: 34135909)
      EMBO J. 2021 Sep 1;40(17):e106320. (PMID: 34260075)
      Ageing Res Rev. 2021 Jul;68:101317. (PMID: 33711509)
      Evid Based Complement Alternat Med. 2022 Oct 14;2022:1052359. (PMID: 36276863)
      Biomed Pharmacother. 2019 Mar;111:315-324. (PMID: 30590319)
      J Alzheimers Dis. 2020;76(4):1199-1213. (PMID: 32597798)
      Cell Res. 2019 Oct;29(10):787-803. (PMID: 31488882)
      Sci Rep. 2022 Jun 30;12(1):11065. (PMID: 35773306)
      Front Neurosci. 2020 Dec 18;14:602508. (PMID: 33390886)
      J Neuroimmunol. 2020 Jun 23;346:577284. (PMID: 32652366)
      Oxid Med Cell Longev. 2021 Jul 8;2021:5525306. (PMID: 34306309)
      Lancet Neurol. 2022 Aug;21(8):726-734. (PMID: 35643092)
      Pharmacol Ther. 2022 Mar;231:107978. (PMID: 34492236)
      J Ethnopharmacol. 2021 Apr 6;269:113725. (PMID: 33352241)
      Mol Nutr Food Res. 2020 Jan;64(2):e1900636. (PMID: 31835282)
      Cell. 2018 Sep 6;174(6):1388-1405.e21. (PMID: 30193112)
      J Allergy Clin Immunol. 2022 Sep;150(3):513-522. (PMID: 36075637)
      Oxid Med Cell Longev. 2020 Sep 10;2020:4754195. (PMID: 32963694)
      Transl Psychiatry. 2019 Aug 5;9(1):189. (PMID: 31383855)
      J Alzheimers Dis. 2018;63(4):1337-1346. (PMID: 29758946)
      Gut. 2020 Feb;69(2):283-294. (PMID: 31471351)
      Brain Behav Immun. 2021 Jul;95:330-343. (PMID: 33839232)
      Life Sci. 2021 Dec 15;287:120088. (PMID: 34715145)
      Aging (Albany NY). 2020 Mar 19;12(6):5539-5550. (PMID: 32191919)
      Alzheimers Dement. 2022 Apr;18(4):700-789. (PMID: 35289055)
      J Alzheimers Dis. 2018;64(s1):S107-S117. (PMID: 29562523)
      Neurotox Res. 2017 Apr;31(3):327-333. (PMID: 27913964)
      J Clin Invest. 2021 Jul 1;131(13):. (PMID: 34196307)
      Nutrients. 2021 Jan 25;13(2):. (PMID: 33504065)
      Front Psychiatry. 2022 Apr 27;13:879491. (PMID: 35573324)
      Front Aging Neurosci. 2017 Jun 20;9:195. (PMID: 28676754)
      J Alzheimers Dis. 2017;60(4):1241-1257. (PMID: 29036812)
      Neurobiol Aging. 2020 Aug;92:114-134. (PMID: 32417748)
      J Alzheimers Dis. 2022;86(4):1501-1526. (PMID: 35213369)
    • Accession Number:
      0 (tau Proteins)
      0 (Toll-Like Receptor 4)
      0 (NF-kappa B)
      5W494URQ81 (Streptozocin)
      0 (Myeloid Differentiation Factor 88)
      0 (Occludin)
      0 (RNA, Ribosomal, 16S)
      0 (Tlr4 protein, mouse)
    • Publication Date:
      Date Created: 20230602 Date Completed: 20230605 Latest Revision: 20230620
    • Publication Date:
      20240829
    • Accession Number:
      PMC10237464
    • Accession Number:
      10.1371/journal.pone.0286086
    • Accession Number:
      37267300