| 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 |
Abstract 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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