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| Author(s): |
Fernanda Machado Chaves
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) |
| Defense date: | 2021-06-15 |
| Examining board members: |
José Donato Júnior;
Luiz Osório Silveira Leiria;
Roberto de Pasquale;
Cleyton Roberto Sobrinho
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| Advisor: | José Donato Júnior; Renata Frazão |
| Abstract | |
The hypothalamus plays an important role in body homeostasis. Inflammatory cytokines can provide changes in energy homeostasis, influencing food intake. We performed electrophysiological records to investigate the acute effects of tumor necrosis factor alpha (TNF- alpha), interleukin-6 (IL-6), and interleukin-1beta (IL-1beta), on the excitability of the membrane of neurons expressing the agouti-related protein (AgRP) or proopiomelanocortin (POMC) producing neurons of the arched nucleus of the hypothalamus (ARH). We found that TNF- alpha and IL-1beta induce acute inhibition in the electrical activity of 35-42% of cells expressing AgRP in ARH. IL-6 did not induce acute changes in the activity of the studied neurons. Co-infusion of IL-6 did not affect the general IL-1beta-induced response in the activity of AgRP neurons. Our results indicate that the effect of TNF- alpha and IL-1beta especially on the activity of AgRP-producing neurons contributes to inflammation-induced anorexia observed during acute inflammatory conditions. In the second part of the thesis, we evaluated the importance of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) on neurons that express somatostatin (SST). GH receptor expression in the brain is important to allow neuroendocrine neurons to detect GH levels and regulate GH hypophysis secretion by negative feedback. The somatotrophic axis consists mainly of neurons that express GH-releasing hormone (GHRH) and SST. GHRH and SST regulate positively and negatively, respectively, the synthesis and release of physiatry GH. To understand how GH promotes such actions, we evaluate dwellers in mice the effects induced by selective ablation of the IGF-1 and GH and IGF-1 receptors, exclusively in neurons expressing SST. Surprisingly, our results showed that selective deletion of both IGF-1 receptor and GH and IGF-1 receptors did not promote growth changes in energy metabolism and IGF-1 secretion between groups, both in males and females. Therefore, SST neurons may not be the place where negative feedback happens. These results contribute to the understanding of the physiological importance of cytokine action and growth factors on the activity of hypothalamic neurons and in the neuroendocrine control of metabolism. (AU) | |
| FAPESP's process: | 17/21854-9 - Investigation of pro- and anti-inflamatory cytokines in biophysical properties of POMC and AgRP neurons of the arcuate nucleus of the hypothalamus |
| Grantee: | Fernanda Machado Chaves |
| Support Opportunities: | Scholarships in Brazil - Doctorate |