Heterogeneity of NG2 and astroglial functional domains: application on dysfunctions of dopaminergic system

• Grant number: 17/23737-0
• Support Opportunities: Scholarships abroad - Research Internship - Scientific Initiation
• Start date: January 15, 2018
• End date: March 14, 2018
• Field of knowledge: Biological Sciences - Physiology
• Principal Investigator: Elaine Aparecida Del Bel Belluz Guimarães
• Grantee: Gabrielli Caroline Leal-Luiz
• Supervisor: Laura Lopez Mascaraque
• Host Institution: Faculdade de Odontologia de Ribeirão Preto (FORP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: Instituto Cajal, Spain

Abstract

Neuron's environment affected in a cascade of processes is collectively termed as neuroinflammation. About this, the neuroinflammatory component of neurodegenerative disorders comprises robust activation of the resident glial cell. In this sense, astrocytes are essential mediators in the homeostasis of the extracellular environment of neurons. Their role within the brain, however, may be either protective or detrimental. While certain neurodegenerative diseases may be caused by astrocytes hyperactivation, they may also inhibit oxidative stress, prevent mitochondrial damage and produce neurotrophic factors. Regarding another type of glial cell, oligodendrocytes have as the predominant function the insulation of axons in the central nervous system (CNS). They are responsible for the synthesis and installation of myelin, which surrounds the axons in the CNS. Some studies have revealed the oligodendrocytes as a key in determined neurodegenerative diseases. Recently, a population of non-neuronal cells, the NG2 cells, attracts the attention of scientists. Stallcup and Cohn have first described the chondroitin sulfate proteoglycan expressed in rat oligodendrocyte progenitor cells (OPCs). Later, the NG2 molecule was also found to be expressed in several other cells or tissues during development, including the vascular system, skeletal and cardial myoblasts, chondroblasts and different human tumors. In the CNS, Butt et al. described them as 'synantocytes'-the fifth type or the fourth major type of glial cells. In this sense, NG2-glia or polydendrocytes are the most enigmatic population in the brain, making up <5-15% of all CNS cells. These cells, described three decades ago, are defined by their branched morphology and expression of both NG2-proteoglycan and ±-type platelet-derived growth-factor-receptor (PDGFR-±). It is clear the role of astrocytes and NG2 cells in pathologies related to CNS. The research project related with this scholarship application has searched the neural mechanisms about 5-lipoxygenase (an enzyme that act on the synthesis of leukotrienes) actuation on the dopaminergic modulation of the motor system. Regarding this, glial cells participation could provide a new mechanism target for 5-lipoxygenase central effect. Besides, the neuroinflammatory process in neurodegenerative diseases, mainly represented by glial actuation, is a valorous theme for increment the study focus of thematic project related to the present research project. (AU)