Central growth hormone action regulates neuroglial and proinflammatory markers in the hypothalamus of male mice

Autor(es)

Wasinski, Frederick ; Tavares, Mariana R. ; Gusmao, Daniela O. ; List, Edward O. ; Kopchick, John J. ; Alves, Guilherme A. ; Frazao, Renata ; Donato Jr, Jose

• Tipo de documento: Artigo Científico
• Fonte: Neuroscience Letters; v. 806, p. 8-pg., 2023-04-11.

Resumo

Growth hormone (GH) action in specific neuronal populations regulates neuroendocrine responses, metabolism, and behavior. However, the potential role of central GH action on glial function is less understood. The present study aims to determine how the hypothalamic expression of several neuroglial markers is affected by central GH action in male mice. The dwarf GH- and insulin-like growth factor-1 (IGF-1)-deficient Ghrhrlit/lit mice showed decreased mRNA expression of Nes (Nestin), Gfap, Iba1, Adgre1 (F4/80), and Tnf (TNF alpha) in the hypothalamus, compared to wild-type animals. In contrast, transgenic overexpression of GH led to high serum GH and IGF-1 levels, and increased hypothalamic expression of Nes, Gfap, Adgre1, Iba1, and Rax. Hepatocyte-specific GH receptor (GHR) knockout mice, which are characterized by high serum GH levels, but reduced IGF-1 secretion, showed increased mRNA expression of Gfap, Iba1, Tnf, and Sox10, demonstrating that the increase in GH levels alters the hypothalamic expression of glial markers associated with neuroinflammation, independently of IGF-1. Conversely, brain-specific GHR knockout mice showed reduced expression of Gfap, Adgre1, and Vim (vimentin), indicating that brain GHR signaling is necessary to mediate GH-induced changes in the expression of several neuroglial markers. In conclusion, the hypothalamic mRNA levels of several neuroglial markers associated with inflammation are directly modulated by GHR signaling in male mice. (AU)

• Processo FAPESP: 19/21707-1 - Influência da privação alimentar na excitabilidade de neurônios que expressam o gene Kiss1
• Beneficiário: Renata Frazão
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 19/07005-4 - Participação do receptor B2 de cinina no sistema nervoso com ênfase no circuito dopaminérgico
• Beneficiário: Frederick Wasinski
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 20/10102-9 - Estudo dos efeitos induzidos pela ablação do receptor de GH em neurônios da área hipotalâmica lateral
• Beneficiário: Mariana Rosolen Tavares
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 20/01318-8 - Sistema nervoso central como um alvo do hormônio do crescimento para a regulação de múltiplas funções biológicas
• Beneficiário: Jose Donato Junior
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 21/03316-5 - Avaliação da importância da transmissão GABAérgica e dopaminérgica sobre os neurônios que expressam o hormônio liberador de GH para o controle da secreção de GH
• Beneficiário: Daniela de Oliveira Gusmão
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado