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Role of orexin neurons in the perifornicial region of the hypothalamus (PeF/LH) in respiratory control produced by central chemoreflex activation during sleep and wakefulness rats

Grant number: 12/13713-2
Support type:Scholarships abroad - Research Internship - Doctorate
Effective date (Start): January 03, 2013
Effective date (End): May 02, 2013
Field of knowledge:Biological Sciences - Physiology
Principal Investigator:Thiago dos Santos Moreira
Grantee:Rosélia dos Santos Damasceno
Supervisor abroad: Eugene E. Nattie
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Local de pesquisa : Dartmouth College, United States  
Associated to the scholarship:10/15692-7 - Involvement of the Kolliker-Fuse in cardiorespiratory control during activation of central and peripheral chemoreceptors, BP.DR

Abstract

The orexins neuropeptides are classified as consisting of two subtypes, orexin-orexin-A and B derived from the same precursor (pre-pro-orexin) and bind to two G protein-coupled receptors: a receiver (OX1R) selective for orexin-A and receptor 2 (OX2R) for orexin A and B. The orexinergic neurons are located exclusively in the dorsal and lateral hypothalamic and area perifornicial. This region has large projections and is associated with multiple functions such as control of homeostasis, feeding behavior, reward processes, sleep-wake states, stress responses, nociception and cardiovascular and respiratory control. Recent studies have support the hypothesis that orexin plays a role in the control of breathing and central chemoreception. Projections of hypothalamic orexinergic neurons are found in regions of the brainstem involved in breathing control, including the rostral ventrolateral medulla, raphe, locus coeruleus, Kölliker-Fuse, nucleus of the solitary tract (NTS), dorsal motor nucleus of the vagus, motor abstract nucleus of the hypoglossal and phrenic motor nucleus (Marcus et al., 2001, Young et al, 2005; Nixon & Smale, 2007; Kuwaki, 2008; Tsujino & Sakurai, 2009). Therefore, this project will inhibit pre-mRNA pro-orexin, the precursor of orexin A and B, specifically in orexinergic neurons of perifornicial region and lateral hypothalamus (PeF-LH) and evaluate the effects on respiration and central chemoreflex in awake rats and during sleep. We will apply an interfering RNA (siRNA) to inhibit the synthesis of orexins and we will assess the ventilation, metabolic rate, body temperature before and during the inhibition. (AU)