Abstract
Background: The orexinergic (OXergic) system contributes to the defense system. It has also been reported that the degeneration of OXergic neurons occurs during sepsis. Thus, the decline of OXergic activity may contribute to impairment of the defense system in sepsis. In this study, we determined whether: (i) lipopolysaccharide (LPS) reduces the brain orexin A (OXA) content and (ii) the OXergic system contributes to survival from sepsis in rats. Methods: With approval of our protocol by our University Animal Ethics Committee, OX neuron-ablated (OX/ataxin-3 transgenic [OX/AT3 TG]) and wild-type Sprague-Dawley rats, weighing 250–350 g, were used. LPS (10 mg/kg) was administered intraperitonally to the wild-type rats (group SD, n = 26) and OX/AT3 TG rats (group TG, n = 14). Another 7 SD rats were included as a saline control (group C). Survival analysis was then performed over a period of 3 days. All surviving rats were decapitated and the brain OXA contents (from the cerebrocortex, hippocampus, hypothalamus, and pons) were quantified using ELISA kits. Results: In group SD, 61.5% rats survived, while in group TG, only 21.4% survived (p < 0.05). LPS significantly reduced OXA content (pg/mg of tissue) in group SD (2.92 ± 0.38) compared to in group C (4.10 ± 1.21) in the pons (p < 0.05). OXA content in group TG was substantially lower than in group C and group SD in all brain regions. Conclusions: LPS significantly reduced OXA contents in the pons which contains the locus coeruleus to regulate sympathetic activity in the defense system.
