| Full text | |
| Author(s): |
Passaglia, Patricia
;
Kanashiro, Alexandre
;
Silva, Hadder Batista
;
Navegantes, Luiz Carlos Carvalho
;
Lacchini, Riccardo
;
Carnio, Evelin Capellari
;
Branco, Luiz G. S.
Total Authors: 7
|
| Document type: | Journal article |
| Source: | BRAIN BEHAVIOR AND IMMUNITY; v. 119, p. 15-pg., 2024-04-03. |
| Abstract | |
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 proinflammatory profile in the intestine and reduced the serum concentration of tryptophan and serotonin (5HT), 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 antiinflammatory 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. (AU) | |
| FAPESP's process: | 16/17681-9 - Pathophysiological changes during systemic inflammation |
| Grantee: | Luiz Guilherme de Siqueira Branco |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 20/12777-3 - "Interaction between Angiotensin-converting enzyme 2 and serotonin during systemic inflammation" |
| Grantee: | Patrícia Passaglia |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |