Sexual dimorphism of hypothalamic serotonin release during systemic inflammation: Role of endothelin-1

The hypothalamus receives serotonergic projections from the raphe nucleus in a sex-specific manner. During systemic inflammation, hypothalamic levels of serotonin (5-hydroxytryptamine [5-HT]) decrease in male rats. The present study evaluated the involvement of endothelin-1 (ET-1) in the febrile res...

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Bibliographic Details
Published in:Journal of neuroimmunology 2024-09, Vol.394, p.578427, Article 578427
Main Authors: Costa, Regina Azevedo, Amatnecks, Jefferson Angulski, de Oliveira Guaita, Gisele, Stern, Cristina Aparecida Jark, Branco, Luiz Guilherme Siqueira, Zampronio, Aleksander Roberto
Format: Article
Language:English
Subjects:
Febrile response
Hypolocomotion
Hypothalamus
Lipopolysaccharide
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Summary:The hypothalamus receives serotonergic projections from the raphe nucleus in a sex-specific manner. During systemic inflammation, hypothalamic levels of serotonin (5-hydroxytryptamine [5-HT]) decrease in male rats. The present study evaluated the involvement of endothelin-1 (ET-1) in the febrile response, hypolocomotion, and changes in hypothalamic 5-HT levels during systemic inflammation in male and female rats. An intraperitoneal injection of lipopolysaccharide (LPS) induced a febrile response and hypolocomotion in both male and female rats. However, although LPS reduced hypothalamic levels of 5-HT and its metabolite 5-hydroxyindol acetic acid (5-HIAA) in male rats, it increased these levels in female rats. An intracerebroventricular injection of the endothelin-B receptor antagonist BQ788 significantly reduced LPS-induced fever and hypolocomotion and changes in hypothalamic 5-HT and 5-HIAA levels in both male and female rats. The i.c.v. administration of ET-1 induced a significant fever and hypolocomotion, but reduced the hypothalamic levels of 5-HT and 5-HIAA in both males and females. These results suggest an important sexual dimorphism during systemic inflammation regarding the release of 5-HT in the hypothalamus. Moreover, ET-1 arises as an important mediator involved in the changes in hypothalamic 5-HT levels in both male and female rats. •Hypothalamic serotonin levels are reduced in male rats during systemic inflammation.•However, in females, hypothalamic serotonin levels are increased after lipopolysaccharide injection.•The febrile response and hypolocomotion are similar in both in male and female rats.•Endothelin-1, through ETB receptors, seems to be involved in the changes in hypothalamic serotonin levels.
ISSN:0165-5728
1872-8421
1872-8421
DOI:10.1016/j.jneuroim.2024.578427