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

IF 2.9 4区医学 Q3 IMMUNOLOGY Journal of neuroimmunology Pub Date : 2024-08-03 DOI:10.1016/j.jneuroim.2024.578427

Regina Azevedo Costa , Jefferson Angulski Amatnecks , Gisele de Oliveira Guaita , Cristina Aparecida Jark Stern , Luiz Guilherme Siqueira Branco , Aleksander Roberto Zampronio

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Abstract

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.

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系统性炎症期间下丘脑血清素释放的性别双态性：内皮素-1的作用

下丘脑以性别特异性的方式接受来自剑突核的血清素能投射。在全身炎症期间，雄性大鼠下丘脑的血清素（5-羟色胺 [5-HT]）水平会下降。本研究评估了内皮素-1（ET-1）在雄性和雌性大鼠发热反应、下丘脑运动和全身炎症期间下丘脑 5-HT 水平变化中的参与情况。腹腔注射脂多糖（LPS）可诱发雄性和雌性大鼠的发热反应和运动减退。然而，虽然 LPS 降低了雄性大鼠下丘脑中 5-HT 及其代谢产物 5- 羟基吲哚乙酸（5-HIAA）的水平，但却提高了雌性大鼠的这些水平。脑室内注射内皮素-B 受体拮抗剂 BQ788 可显著降低 LPS 诱导的发热和下丘脑运动，并减少雄性和雌性大鼠下丘脑 5-HT 和 5-HIAA 水平的变化。静注 ET-1 可诱导雄性和雌性大鼠明显发热和下丘脑运动，但会降低下丘脑 5-HT 和 5-HIAA 的水平。这些结果表明，在全身性炎症期间，下丘脑中的 5-HT 释放存在重要的性双态性。此外，ET-1 是参与雄性和雌性大鼠下丘脑 5-HT 水平变化的重要介质。

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来源期刊

Journal of neuroimmunology 医学-免疫学

CiteScore

6.10

自引率

3.00%

发文量

154

审稿时长

37 days

期刊介绍： The Journal of Neuroimmunology affords a forum for the publication of works applying immunologic methodology to the furtherance of the neurological sciences. Studies on all branches of the neurosciences, particularly fundamental and applied neurobiology, neurology, neuropathology, neurochemistry, neurovirology, neuroendocrinology, neuromuscular research, neuropharmacology and psychology, which involve either immunologic methodology (e.g. immunocytochemistry) or fundamental immunology (e.g. antibody and lymphocyte assays), are considered for publication.