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

Author(s)

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

• Document type: Journal article
• Source: Neuroscience Letters; v. 806, p. 8-pg., 2023-04-11.

Abstract

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)

• FAPESP's process: 19/21707-1 - Food deprivation effects in kisspeptin neurons excitability
• Grantee: Renata Frazão
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/07005-4 - Kinin receptor B2 participation in the nervous system with emphasis on the dopaminergic circuit
• Grantee: Frederick Wasinski
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 20/10102-9 - Study of the effects induced by GH receptor ablation in neurons of the lateral hypothalamic area
• Grantee: Mariana Rosolen Tavares
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 20/01318-8 - Central nervous system as a target of growth hormone for the regulation of multiple biological functions
• Grantee: Jose Donato Junior
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 21/03316-5 - Evaluation of the importance of GABAergic and dopaminergic transmission in neurons that express the growth hormone-releasing hormone to the control of GH secretion
• Grantee: Daniela de Oliveira Gusmão
• Support Opportunities: Scholarships in Brazil - Post-Doctoral