Central serotonin prevents hypotension and hypothermia and reduces plasma and spleen cytokine levels during systemic inflammation

Autor(es)

Mota, Clarissa M. D. ^[1] ; Borges, Gabriela S. ^[1] ; Amorim, Mateus R. ^[2] ; Carolino, Ruither O. G. ^[2] ; Batalhao, Marcelo E. ^[3] ; Anselmo-Franci, Janete A. ^{[2, 1]} ; Carnio, Evelin C. ^[3] ; Branco, Luiz G. S. ^{[2, 1]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Med Sch Ribeirao Preto, Dept Physiol, Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Dent Sch Ribeirao Preto, Dept Morphol Physiol & Basic Pathol, Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Nursing Sch Ribeirao Preto, Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: BRAIN BEHAVIOR AND IMMUNITY; v. 80, p. 255-265, AUG 2019.
• Citações Web of Science: 0

Resumo

An exceptionally high mortality rate is observed in sepsis and septic shock. Systemic administration of lipopolysaccharide (LPS) has been used as an experimental model for sepsis resulting in an exacerbated immune response, brain neurochemistry adjustments, hypotension, and hypothermia followed by fever. Central serotonergic pathways not only modulate systemic inflammation (SI) but also are affected by SI, including in the anteroventral region of the hypothalamus (AVPO), which is the hierarchically most important region for body temperature (Tb) control. In this study, we sought to determine if central serotonin (5-HT) plays a role in SI induced by intravenous administration of LPS (1.5 mg/kg) in male Wistar rats (280-350 g) by assessing 5-HT levels in the AVPO, mean arterial pressure, heart rate, and Tb up to 300 min after LPS administration, as well as assessing plasma and spleen cytokine levels, nitric oxide (NO) plasma levels, and prostaglandin (PG) E-2 levels in the AVPO at 75 min and 300 min after LPS administration. We observed reduced AVPO 5-HT levels, hypotension, tachycardia, hypothermia followed by fever, as well as observing increased plasma NO, plasma and spleen cytokines and AVPO PGE(2) levels in SI. Intracerebroventricular (icy) administration of 5-HT 30 min before LPS administration prevented hypotension and hypothermia, which were accompanied by reduced plasma NO, as well as plasma TNF-alpha, IL-1 beta, IL-6, and IL-10 and spleen TNF-alpha and IL-10 levels. We suggest that SI reduced 5-HT levels in the AVPO favor an increased pro-inflammatory status both centrally and peripherally that converge to hypotension and hypothermia. Moreover, our results are consistent with the notion that exogenous 5-HT given icy prevents hypotension and hypothermia probably activating the splenic anti-inflammatory pathway. (AU)

• Processo FAPESP: 17/09878-0 - Efeito da estimulação vagal durante desafio imune por LPS em ratos normotensos e espontaneamente hipertensos
• Beneficiário: Mateus Ramos Amorim
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 16/17681-9 - Alterações fisiopatológicas durante a inflamação sistêmica
• Beneficiário: Luiz Guilherme de Siqueira Branco
• Modalidade de apoio: Auxílio à Pesquisa - Temático