دورية أكاديمية
Diminazene aceturate attenuates systemic inflammation via microbiota gut-5-HT brain-spleen sympathetic axis in male mice.
| العنوان: | Diminazene aceturate attenuates systemic inflammation via microbiota gut-5-HT brain-spleen sympathetic axis in male mice. |
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| المؤلفون: | Passaglia P; Department of Oral and Basic Biology Ribeirão Preto, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil. Electronic address: ppassaglia@usp.br., Kanashiro A; Department of Psychiatry and Behavioral Sciences, Translational Psychiatry Program, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA., Batista Silva H; Department of General Nursing, School of Nursing of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil., Carlos Carvalho Navegantes L; Department of Physiology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil., Lacchini R; Department of Psychiatric Nursing and Human Sciences, School of Nursing of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil., Capellari Cárnio E; Department of General Nursing, School of Nursing of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil., Branco LGS; Department of Oral and Basic Biology Ribeirão Preto, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil; Department of Physiology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil. Electronic address: branco@forp.usp.br. |
| المصدر: | Brain, behavior, and immunity [Brain Behav Immun] 2024 Jul; Vol. 119, pp. 105-119. Date of Electronic Publication: 2024 Mar 27. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: Netherlands NLM ID: 8800478 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2139 (Electronic) Linking ISSN: 08891591 NLM ISO Abbreviation: Brain Behav Immun Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: <2000- > : Amsterdam : Elsevier Original Publication: San Diego : Academic Press, [c1987- |
| مواضيع طبية MeSH: | Spleen*/metabolism , Spleen*/drug effects , Diminazene*/analogs & derivatives , Diminazene*/pharmacology , Lipopolysaccharides*/pharmacology , Mice, Inbred C57BL* , Gastrointestinal Microbiome*/drug effects , Inflammation*/metabolism , Serotonin*/metabolism , Sympathetic Nervous System*/drug effects , Sympathetic Nervous System*/metabolism , Endotoxemia*/metabolism, Animals ; Male ; Mice ; Brain/metabolism ; Brain/drug effects ; Brain-Gut Axis/drug effects ; Anti-Inflammatory Agents/pharmacology ; Tumor Necrosis Factor-alpha/metabolism |
| مستخلص: | The sympathetic arm of the inflammatory reflex is the efferent pathway through which the central nervous system (CNS) can control peripheral immune responses. Diminazene aceturate (DIZE) is an antiparasitic drug that has been reported to exert protective effects on various experimental models of inflammation. However, the pathways by which DIZE promotes a protective immunomodulatory effects still need to be well established, and no studies demonstrate the capacity of DIZE to modulate a neural reflex to control inflammation. C57BL/6 male mice received intraperitoneal administration of DIZE (2 mg/Kg) followed by lipopolysaccharide (LPS, 5 mg/Kg, i.p.). Endotoxemic animals showed hyperresponsiveness to inflammatory signals, while those treated with DIZE promoted the activation of the inflammatory reflex to attenuate the inflammatory response during endotoxemia. The unilateral cervical vagotomy did not affect the anti-inflammatory effect of DIZE in the spleen and serum. At the same time, splenic denervation attenuated tumor necrosis factor (TNF) synthesis in the spleen and serum. Using broad-spectrum antibiotics for two weeks showed that LPS modulated the microbiota to induce a pro-inflammatory profile in the intestine and reduced the serum concentration of tryptophan and serotonin (5-HT), while DIZE restored serum tryptophan and increased the hypothalamic 5-HT levels. Furthermore, the treatment with 4-Chloro-DL-phenylalanine (pcpa, an inhibitor of 5-HT synthesis) abolished the anti-inflammatory effects of the DIZE in the spleen. Our results indicate that DIZE promotes microbiota modulation to increase central 5-HT levels and activates the efferent sympathetic arm of the inflammatory reflex to control splenic TNF production in endotoxemic mice. Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2024 Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Diminazene aceturate; Inflammatory reflex; Lipopolysaccharide; Microbiota gut-brain-spleen axis; Serotonin; Systemic inflammation |
| المشرفين على المادة: | JI8SAD85NO (diminazene aceturate) Y5G36EEA5Z (Diminazene) 0 (Lipopolysaccharides) 333DO1RDJY (Serotonin) 0 (Anti-Inflammatory Agents) 0 (Tumor Necrosis Factor-alpha) |
| تواريخ الأحداث: | Date Created: 20240328 Date Completed: 20240609 Latest Revision: 20240609 |
| رمز التحديث: | 20240610 |
| DOI: | 10.1016/j.bbi.2024.03.037 |
| PMID: | 38548186 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 1090-2139 |
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| DOI: | 10.1016/j.bbi.2024.03.037 |