Presentation
Chronic Exposure to Elevated Ambient CO2 Influences the Orexinergic System in the Lateral Hypothalamus and Dorsocaudal Medulla
Experimental Biology 2016
(2016)
Abstract
Central chemoreceptors (CCRs) of the caudal solitary complex (cSC) are activated by hypercapnic acidosis (HA). CCRs also receive input from orexinergic projections originating in the lateral hypothalamus (LH). Indeed both HA and the neuropeptides orexin A&B stimulate ventilation and gastric acid secretion (Dean 2011 Resp. Physiol. & Neurobiol. 175:189–209). Acute exposure to severe hypercapnia (Wang et al. 2013 Respirology 18:102–107) decreases orexins and increases orexin-1 receptor (OX1) expression in the hypothalamus of mice while OX1 expression in the brain stem remains unchanged. We hypothesized that chronic CO2 retention (e.g., disabled submarines, underventilated workspaces, hypoventilation syndromes) causes changes in the orexinergic system. Given orexins’ roles in arousal, feeding, energy consumption, and respiration-among others, this change could impair health and well being in CO2 retainers. Male Sprague-Dawley rats (~250–300g) were placed in a Biospherix chronic CO2 environmental chamber (66”W×20”D×20”H) equipped with two controllers capable of regulating ambient CO2 at 0.1–4.0% CO2 in air. Rats were placed in the box for 1–4 weeks and fed ad libitum. Chamber humidity and temperature were recorded using the HOBO data logger and ambient CO2 was recorded using Lab Scribe (iWorx). Prior to harvesting brains, rats were transcardially perfused with tomato lectin before perfusion with fixative. Coronal sections representing the LH and cSC were stained with anti-OX1 and GFAP antibodies and examined using confocal microscopy. Rats not perfused with fixative had hypothalamus and brainstem removed for qPCR analysis. To date, we have tested 6 rats in 2% CO2 and 16 rats in 1% CO2 in air for 1–4 weeks. Confocal micrographs of the LH and cSC show a marked increase in neurons expressing OX1 in both regions as early as one week at 2% CO2. Interestingly, we also saw a sensitization of astrocytes to orexin-A indicated by an induction of OX1 expression. Additionally, analysis of qPCR data show marked changes in both neuropeptide and receptor expression in both regions that trend toward normalization at 4 weeks. In conclusion, our findings indicate that chronic exposure to hypercapnia changes expression of both orexins and their receptors in the LH and cSC. These changes presumably modify systems activated by orexins. This includes respiration during sleep and wakefulness; gastric acid secretion and feeding; and even astrocyte activation (Support provided by the ONR Undersea Medicine Program).
Disciplines
Publication Date
April 3, 2016
Location
San Diego, CA
Comments
B614 772.9
Citation Information
J. W. Sherwood, R. S. Beard, C. S. Landon and J. B. Dean. "Chronic Exposure to Elevated Ambient CO2 Influences the Orexinergic System in the Lateral Hypothalamus and Dorsocaudal Medulla" Experimental Biology 2016 (2016) Available at: http://works.bepress.com/richard-beard/11/