Role of O-GlcNAcylation in the neuroinflammatory functions of astrocytes

• Grant number: 19/13829-0
• Support type: Scholarships in Brazil - Doctorate
• Effective date (Start): October 01, 2019
• Effective date (End): July 01, 2023
• Field of knowledge: Biological Sciences - Immunology
• Principal researcher: Thiago Mattar Cunha
• Grantee: Rafaela Mano Guimarães
• Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases, AP.CEPID
• Associated scholarship(s): 21/10477-5 - Regulation of microglial metabolism and the implication in the inflammatory response of astrocytes during Alzheimer's disease, BE.EP.DR

Abstract

Astrocytes are the most abundant glial cells of the Central Nervous System (CNS), essential for the maintenance of brain homeostasis. It has been indisputable the astrocytes participation in experimental models of multiple sclerosis (EAE) and neuropathic pain, in which their activation contribute to the amplification of the inflammatory response. In view of a neuroinflammatory condition, increased glucose uptake by astrocytes provides substrates that can be processed by alternative metabolic pathways, including the hexosamine pathway (HBP). The use of glucose by HBP leads to the formation of a precursor named UDP-N-acetylglucosamine (UDP-GlcNAc) which, by the action of the enzyme O-GlycosylTransferase (OGT), generates post-translational modifications called O-GlcNAcylation. The occurrence of O-GlcNAcylation has been recently associated with the development of neurodegenerative diseases, as well as activation of macrophages and T lymphocytes. Previous unpublished observation from our research group has demonstrated that astrocytes are the main cells expressing OGT in the steady-state CNS. Therefore, knowing the relevance of astrocytes in EAE and neuropathic pain models and the participation of O-GlcNAcylation in inflammation, here we aim to investigate how the modulation of OGT and OGT-dependent post-translational modifications can modulate the astrocyte function under neuroinflammatory context. In order to address this aim, we will use pharmacological and molecular tools to modulate OGT expression and activity in vitroand in vivo (EAE and neuropathic pain models). The results obtained in this project could be used as a basis for the development of new therapeutic targets aiming the treatment of neuroinflammatory diseases. (AU)

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)

ANIBAL SILVA, CONCEICAO ELIDIANNE; GUIMARAES, RAFAELA MANO; CUNHA, THIAGO MATTAR. Sensory neuron-associated macrophages as novel modulators of neuropathic pain. PAIN REPORTS, v. 6, n. 1, 2021. (20/05446-0, 13/08216-2, 19/13829-0, 17/50419-9)