The role of astrocytes on neonatal nutritional programming in mice

• Grant number: 17/23946-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2018
• End date: March 31, 2019
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Lucila Leico Kagohara Elias
• Grantee: Erick Cabral Moreti
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

There is an increasing in the prevalence rate of obesity in the world. The prevalence of obesity-related chronic diseases, such as diabetes and ischemic heart disease is also increasing. Several evidence points out to the association of development of obesity, metabolic syndrome and chronic diseases and the nutritional conditions during the pre- and neonatal period, suggesting the existence of a nutritional programming process. The hypothalamus, mainly the arcuate nucleus, plays a central role in the control of energy homeostasis, an action mediated by hormones, with emphasis on leptin, that act on neurons that express anorexigenic and orexigenic neuropeptides. Astrocytes have been also implicated in the control of energy homeostasis. Astrocytes possess a role in neuronal sustentation and nutrition, blood flow regulation in the brain, blood-brain barrier control and synapses formation and maintenance and express leptin receptors (LEPR). In high-fat diet models the development of hypothalamic inflammation was associated with high levels of circulating leptin and TLR4 pathway activation in neurons and astrocytic cells, changes in astrocyte morphology and concomitant development of central leptin resistance. Experiments with mice indicated that the GFAP expression, an astrocytes marker, is altered with nutritional programming in pre- and postnatal period. Thus, the present study will use the variation in the litter size, therefore, the availability of food in the lactation during the neonatal period and its impact on body weight and food intake in juvenile and adult life. To analyse the role of astrocytes in this process, we will assess the astrocyte morphology and the expression of genes related with leptin action in this cells and hypothalamic inflammation. (AU)