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Role of serotonin in the preoptic area in the modulation of body temperature and nociception during systemic inflammation

Grant number: 17/01633-8
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): November 01, 2017
Effective date (End): November 30, 2019
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:Luiz Guilherme de Siqueira Branco
Grantee:Clarissa Maria Dias Mota
Host Institution: Faculdade de Odontologia de Ribeirão Preto (FORP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:16/17681-9 - Pathophysiological changes during systemic inflammation, AP.TEM
Associated scholarship(s):17/24232-9 - Spinal 5-hydroxytryptamine (5-HT) receptors and activation of brown adipose tissue during systemic inflammation, BE.EP.DR


Inflammation is a sign of neuroimmune interaction acting in the host defense, inducing the production of inflammatory mediators, fever and pain. These conditions are mimicked by Systemic Inflammation (SI) induced by lipopolysaccharide (LPS - outer membrane component of gram-negative bacteria). Fever results from the activation of thermoregulatory neurons in the anteroventral region of the preoptic area of the hypothalamus (AVPO) that also seems to act in the modulation of nociceptive pathways. Serotonin (5-HT) is involved in several neural circuits that maintain homeostasis and is one of the neurotransmitters acting in AVPO, being a potential neuromodulator involved in the control of SI. The present study aims to characterize the mechanisms by which the serotonergic system acts in the modulation of SI. For this purpose, male Wistar rats (250-350 g) will be submitted to LPS-induced immune challenge (100 ¼g/kg) and to experimental protocols: (1) core temperature (Tc) recording and dosage of the levels of plasma corticosterone, 5-HT and its main metabolite in the AVPO; (2) Tc recording in animals submitted to central microinjection of vehicle or 5-HT (doses of 5, 10 or 40 ¼g/¼L); (3) dosages of prostaglandins E2 (PGE2) and D2 (PGD2) in the AVPO, plasma corticosterone and cytokines; (4) thermographic images to assess the heat loss index by the tail; (5) nociceptive sensitivity tests; (6) immunodetection of COX2, phospho-IKK±/², phospho-Akt, phospho-GSK3² and phospho-CREB by western blotting and PGE2 dosage by ELISA to identify the signaling of LPS-induced nociception in the dorsal horn of the spinal cord and in the dorsal root ganglia. This study will clarify the role of the serotonergic system and its therapeutic potential in neuroimmune interactions during SI. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
AMORIM, MATEUS R.; DE DEUS, JUNIA L.; CAZUZA, RAFAEL A.; MOTA, CLARISSA M. D.; DA SILVA, LUIZ E. V.; BORGES, GABRIELA S.; BATALHAO, MARCELO E.; CARNIO, EVELIN C.; BRANCO, LUIZ G. S.. Neuroinflammation in the NTS is associated with changes in cardiovascular reflexes during systemic inflammation. JOURNAL OF NEUROINFLAMMATION, v. 16, . (17/09878-0, 17/01633-8, 16/17681-9)
NOGUEIRA, JONATAS E.; AGOSTINHO, BRENDA K. L.; MOTA, CLARISSA M. D.; BRANCO, LUIZ G. S.. Splenic anti-inflammatory reflex in immune tolerance. Journal of Thermal Biology, v. 85, . (17/01633-8, 16/17681-9)
MOTA, CLARISSA M. D.; ANTUNES-RODRIGUES, JOSE; BRANCO, LUIZ G. S.. Central fractalkine stimulates central prostaglandin E-2 production and induces systemic inflammatory responses. Brain Research Bulletin, v. 140, p. 311-317, . (17/01633-8, 16/17681-9)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
MOTA, Clarissa Maria Dias. Thermoregulatory and neuroimmunomodulatory effects of serotonin. 2019. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) Ribeirão Preto.

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