Effects of kinin B2 receptor deletion on GABAergic neurons and neurons expressing the dopaminergic D2 receptor

• Grant number: 23/09878-0
• Support Opportunities: Scholarships in Brazil - Support Program for Fixating Young Doctors
• Start date: September 01, 2023
• End date: August 31, 2025
• Field of knowledge: Biological Sciences - Physiology
• Agreement: CNPq
• Principal Investigator: Frederick Wasinski
• Grantee: Mariana Rosolen Tavares
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 23/01250-2 - Effects of kinin B2 receptor deletion on GABAergic neurons and neurons expressing the dopaminergic D2 receptor, AP.R

Abstract

The kallikrein-kinin system is an important endogenous proteolytic system that produces kinin peptides and their derivatives, such as kallidin (LBK) and bradykinin (BK). This system participates in the control of several physiological functions, such as inflammatory response, blood pressure control, among others. Kinins exert their effects through two receptors: B1 and B2. The B2 receptor is the most extensively studied because it is expressed under physiological conditions and controls most of kinin functions. In addition to peripheral tissues, B2 expression also occurs in the central nervous system, especially in hippocampus and olfactory bulb neurons, however the effects of kinins in this tissue are poorly understood. A neuroprotective effect is designated to the B2 receptor, since it acts as a neurogenesis facilitator and cell proliferation inducer. Besides, some evidence points to the role of kinins in other processes controlled by the central nervous system, such as motor activity. To contribute to the investigation of the possible roles of kinins and their B2 receptor in the central nervous system, we intend to generate B2 knockout mice in neurons that express classic neurotransmitters, such as GABA (VGAT BK2 KO), through the Cre-LoxP system, and evaluate which physiological and behavioral aspects will be modulated in these animals from this deletion. Moreover, we intend to investigate the role of this receptor in the dopaminergic circuit, using the same methodology for B2 deletion in neurons that express the dopamine D2 receptor (DRD2Cre BK2 KO). We expect to produce relevant results regarding the participation of the SCC in the central nervous system through a technique that allows us to study specific areas such as GABAergic neurons and dopaminergic areas.