Role of beta-defensins in the modulation of inflammation and memory impairment in hippocampus of aged mice

• Grant number: 17/05257-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: June 01, 2017
• End date: May 31, 2019
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Maria Christina Werneck de Avellar
• Grantee: Ivana Noelia Machado
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

One of the theories on aging and memory impairment is the establishment of a state of systemic inflammatory activation that occurs with age. This condition depends essentially on the dysregulation of the immune system, and an altered redox status during aging. The main mediators of inflammatory responses in the Central Nervous System (CNS) are the microglia, dynamic cells that play pivotal roles in plasticity and immune surveillance; they are densely present in the hippocampus. ²-defensins (DEFBs) are a highly conserved family of cationic antimicrobial and immunomodulatory peptides expressed primarily in epithelial cells from different mammalian tissues. Recently, our research group observed that two DEFBs, DEFB1 and sperm-associated antigen 11C (SPAG11C), are expressed in hippocampal neurons, but not in microglia cells, from adult mouse. Based on these data, we propose that changes in DEFB expression in microglia or/and neurons may contribute to the regulation of neuronal cell injury and death observed in the mouse hippocampus with aging. By this means, we are also hypothesizing that DEFBs might modulate the hippocampal-dependent memory impairment associated with aging. Therefore, our aim in the present project is to understand the role of DEFBs in the modulation of the neuroinflammatory response of the hippocampus and loss of memory in the aging mouse. We will use the natural aging in C57BL/6J mouse, and the senescence-accelerated mouse prone strains as experimental models. Our results will contribute to a better understand of the role and mechanisms by which DEFB may protect neuroinflammatory conditions in the CNS, and help in the development of novel biomarkers or targets for therapeutic strategies to prevent or ameliorate these conditions. (AU)