Physiopathology of CO2 sensitivity: role of locus coeruleus

• Grant number: 20/01702-2
• Support Opportunities: Research Projects - Thematic Grants
• Duration: October 01, 2021 - September 30, 2026
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Principal Investigator: Luciane Helena Gargaglioni Batalhão
• Grantee: Luciane Helena Gargaglioni Batalhão
• Host Institution: Faculdade de Ciências Agrárias e Veterinárias (FCAV). Universidade Estadual Paulista (UNESP). Campus de Jaboticabal. Jaboticabal , SP, Brazil
• Associated researchers: Antonio Egidio Nardi ; Bryan Eric Strauss ; Daniel Penteado Martins Dias ; Hélio Zangrossi Júnior ; Lynn Kristine Hartzler ; Patricia Jensen ; Raphael Escorsim Szawka ; Richard Kinkead
• Associated grant(s): 21/13364-7 - Multi-user equipment approved in grant 2020/01702-2: electrophysiological research microscope, AP.EMU
• Associated scholarship(s): 23/09207-9 - Locus coeruleus and CO2/pH chemosensitivity in mice: evaluation during development, sleep/wake cycle and arousal respons, BP.DR; 22/08430-3 - Effect of estrous cycle on paniconegic response to CO2 in mice., BP.IC; 22/11232-9 - Physiopathology of CO2 sensitivity: role of locus coeruleus, BP.TT; + associated scholarships 21/08968-0 - Behavioral and neuroinflammatory effects caused by a simulated poverty model in mice: implications for panic disorder, BP.PD; 22/05057-0 - Contribution of Locus Coeruleus (LC) glial cells in the cardiorespiratory response to hypercapnia and in the manifestation of CO2-induced panic attacks, BP.PD; 22/02070-5 - PHYSIOPATHOLOGY OF CO2 SENSITIVITY: ROLE OF LOCUS COERULEUS, BP.TT; 21/13618-9 - Participation of calcium-activated potassium channels in respiratory, autonomic and behavioral responses to CO2/pH and in the chemosensitivity of LC neurons, BP.PD - associated scholarships

Abstract

The locus coeruleus (LC) is a sexually dimorphic noradrenergic nucleus that projects throughout the brain and is the main source of central norepinephrine controlling various functions, including central chemoreception. Our group was a pioneer in demonstrating the importance of LC in ventilatory responses to CO2/pH changes in males and females and that the gain of LC neurons depends on age, being larger in young (P10) neonates. It is well known that the imbalance in noradrenergic neurotransmission modulation in this area is implicated in the emergence of numerous psychiatric disorders, including panic disorder. Patients suffering from this disorder have a higher sensitivity to CO2/pH. It is known that the brain detects acid for several reasons besides ventilatory control, and the association between hypercapnia and panic disorders is quite strong. Thus, the present project intends to provide a detailed view of the neuronal and glial factors of the LC that determine the chemosensitive gain to CO2/pH and to identify targets for possible clinical treatments of disorders involving abnormal central detection of CO2. (AU)