Spinal 5-hydroxytryptamine (5-HT) receptors and activation of brown adipose tissue during systemic inflammation

• Grant number: 17/24232-9
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Effective date (Start): September 01, 2018
• Effective date (End): May 31, 2019
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Luiz Guilherme de Siqueira Branco
• Grantee: Clarissa Maria Dias Mota
• Supervisor: Shaun Francis Morrison
• Host Institution: Faculdade de Odontologia de Ribeirão Preto (FORP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Research place: Oregon Health & Science University, United States
• Associated to the scholarship: 17/01633-8 - Role of serotonin in the preoptic area in the modulation of body temperature and nociception during systemic inflammation, BP.DR

Abstract

5-hydroxytryptamine (5-HT) plays key thermoregulatory role acting in the central nervous system (CNS). 5-HT spinal administration results in hypothermia and emerging data demonstrate that activation of 5-HT receptors within the intermediolateral column (IML) of the spinal cord increases the sympathetic outflow to brown adipose tissue (BAT). In agreement, endogenous 5-HT1A and 5-HT7 receptors of the IML are activated and enhance BAT activity during cold-evoked increase in BAT. The increased activity of BAT is also observed after systemic lipopolysaccharide (LPS) administration, which is a component of the cell wall of Gram-negative bacteria that induces immune responses resulting in a febrile response. Considering the absence of sufficient knowledge about the mechanisms involving 5-HT receptors activation in the IML during LPS-induced systemic inflammation, we hypothesized that endogenous activation of spinal 5-HT receptors in the IML enhances sympathetic outflow to BAT, causing BAT thermogenesis, during systemic inflammation. Thus, we will perform two experimental protocols: (1) to determine whether activation of 5-HT receptors within the IML contributes to the sympathetic activation of BAT evoked by systemic inflammation, we propose to compare the LPS-evoked increase in BAT activity before and following spinal microinjections of 5-HT into the T4 IML. Moreover, arterial blood pressure, core temperature (TCORE), brown adipose tissue temperature (TBAT), skin temperature (TSKIN), BAT thermogenesis, and shivering electromyographic (EMG) recordings will be recorded; (2): to determine the specific 5-HT receptor subtype within the spinal cord that would contribute to the sympathetic activation of BAT evoked by the immune challenge, we will use a within-trial design to compare the LPS-evoked BAT sympathetic activation before and following microinjections of 5-HT1A and 5-HT7 receptor antagonists into the T4 IML. Moreover, arterial blood pressure, TCORE, TBAT, TSKIN, BAT thermogenesis, and shivering EMG recordings will be recorded. Eventually, this project will investigate whether the involvement of endogenous activation of spinal 5-HT receptors in the IML contributes to the thermoregulatory activation of BAT during systemic inflammation.

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)

MOTA, CLARISSA M. D.; BRANCO, LUIZ G. S.; MORRISON, SHAUN F.; MADDEN, CHRISTOPHER J.. Systemic serotonin inhibits brown adipose tissue sympathetic nerve activity via a GABA input to the dorsomedial hypothalamus, not via 5HT(1A) receptor activation in raphe pallidus. ACTA PHYSIOLOGICA, NOV 2019. (17/24232-9)

MOTA, CLARISSA M. D.; BRANCO, LUIZ G. S.; MORRISON, SHAUN F.; MADDEN, CHRISTOPHER J.. Systemic serotonin inhibits brown adipose tissue sympathetic nerve activity via a GABA input to the dorsomedial hypothalamus, not via 5HT(1A) receptor activation in raphe pallidus. ACTA PHYSIOLOGICA, v. 228, n. 3, p. 17-pg., 2019-11-01. (17/24232-9)

MOTA, CLARISSA M. D.; MADDEN, CHRISTOPHER J.; MORRISON, SHAUN F.. Systemic Administration of Serotonin Reduces the Excitability of the Raphe Pallidus-Brown Adipose Tissue Sympathetic Nerve Pathway. FASEB JOURNAL, v. 33, p. 2-pg., 2019-04-01. (17/24232-9)