Activation of NTS Neurons by CO2 Receiving Orexinergic Projections under Hyperoxia Conditions.

• Grant number: 25/10358-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2025
• End date: December 31, 2025
• Field of knowledge: Biological Sciences - Morphology - Anatomy
• Principal Investigator: José de Anchieta de Castro e Horta Júnior
• Grantee: Yane dos Santos Araujo
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

The orexinergic neurons of the lateral hypothalamus (LH) secrete orexins A and B, neuropeptides with multiple physiological functions. Their receptors are widely distributed throughout the central nervous system (CNS) and contribute to the modulation of physiological processes, including the regulation of ventilation in a sleep-wake cycle-dependent manner. Orexinergic projections establish communication with chemosensitive nuclei, such as the nucleus of the solitary tract (NTS), which, in addition to intrinsic chemosensitivity, integrates and processes afferent stimuli and is essential for the homeostatic regulation of cardiorespiratory functions-particularly its caudal portion (cNTS). Studies have shown that the expression of orexin A receptors (OX1R) in the NTS influences the ventilatory response to CO¿, especially through neurons that express the paired-like homeobox 2b gene (Phox2b) and OX1R. This study aims to investigate the pattern of activation of NTS neurons receiving orexinergic projections under hypercapnic conditions, with and without inhibition of peripheral chemoreceptors by hyperoxia. The hypothesis is that neuronal activation in the NTS will differ between the proposed conditions. In the present study, immunohistochemistry protocols will be performed on brains of adult male Wistar rats previously exposed to hypercapnic stimuli. The expression of c-fos and orexins A and B in the cNTS will be analyzed, and to allow unambiguous identification of the cells receiving orexinergic projections, the neuronal cell bodies will be labeled using Nissl staining. It is expected that the findings will contribute to a better understanding of the central and peripheral mechanisms involved in respiratory control, with an emphasis on the role of orexinergic signaling in the NTS. (AU)