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| Author(s): |
Clarissa Maria Dias Mota
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | Ribeirão Preto. |
| Institution: | Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) |
| Defense date: | 2019-12-04 |
| Examining board members: |
Luiz Guilherme de Siqueira Branco;
Helio Cesar Salgado;
Aleksander Roberto Zampronio
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| Advisor: | Luiz Guilherme de Siqueira Branco |
| Abstract | |
Serotonin or 5-hydroxytryptamine (5-HT) plays an important role in regulating various physiological mechanisms such as body temperature, immunity, appetite, breathing, sleep, and mood. In addition, 5-HT is important for the treatment of diseases, being extensively studied and used therapeutically in psychiatric disorders. The present study investigated: (Study 1) the effects of 5-HT administered systemically and within the central nervous system (CNS) on thermoregulatory responses, (Study 2) the therapeutic effects of intracerebroventricular (icv) administration of 5-HT during mild systemic inflammation and (Study 3) severe systemic inflammation, as well as the relationship between these effects and the splenic antiinflammatory reflex, including this neurotransmitter as an important communication link between the nervous system and the immune system. The present studies used electrophysiological recording and physiological parameters, intravenous (iv) injections, intracerebral injections within regions of interest or icv in anesthetized or non-anesthetized rats, as well as the quantification of prostaglandins (PG) and neurotransmitters in the anteroventral region of the preoptic area of the hypothalamus (AVPO), plasma nitric oxide (NO), corticosterone, as well as splenic and plasma cytokine levels. The results of Study 1 demonstrate that brown adipose tissue (BAT) sympathetic nerve activity (SNA) and BAT thermogenesis are inhibited by systemic or local administration of 8-OH-DPAT via 5-HT1AR activation in the rostral raphé pallidus (rRPa) during skin cooling. On the other hand, systemic administration of 5-HT activates a neural circuitry that results in GABAAR activation in the dorsomedial hypothalamus (DMH), which inhibits skin cooling-evoked increases in BAT thermogenesis. Additionally, the present study demonstrates that there is a serotonergic tone to sympathetic neurons in the rRPa, activating 5-HT1AR and contributing to the inhibition of BAT SNA and BAT thermogenesis in rats under a warm condition. Taken together, the results of the Studies 2 and 3 demonstrate that icv injection of 5-HT presents systemic antiinflammatory effects, i.e., reduced AVPO PGE2 levels and reduced plasma and spleen cytokine levels. In addition to reducing fever caused by mild systemic inflammation, 5-HT icv prevented severe systemic inflammation-induced hypothermia and hypotension and reduced plasma NO levels. Splenectomy prevented part of the systemic anti-inflammatory effect of 5- HT icv during mild systemic inflammation. Altogether, these results indicate that 5-HT presents cryogenic effects in animals exposed to skin cooling and during mild systemic inflammation, besides tonically activating 5-HT1AR in rRPa neurons contributing to the inhibition of BAT SNA and BAT thermogenesis under a warm condition. Additionally, 5-HT presents important anti-inflammatory effects in two different models of systemic inflammation: mild, which mimics, for example, a response to mild bacterial infection and severe, which mimics endotoxemic shock, possibly via activation of the splenic antiinflammatory reflex. (AU) | |
| FAPESP's process: | 17/01633-8 - Role of serotonin in the preoptic area in the modulation of body temperature and nociception during systemic inflammation |
| Grantee: | Clarissa Maria Dias Mota |
| Support Opportunities: | Scholarships in Brazil - Doctorate |