Impact of facial conformation on canine health: Brachycephalic Obstructive Airway Syndrome

The domestic dog may be the most morphologically diverse terrestrial mammalian species known to man; pedigree dogs are artificially selected for extreme aesthetics dictated by formal Breed Standards, and breed-related disorders linked to conformation are ubiquitous and diverse. Brachycephaly–foreshortening of the facial skeleton–is a discrete mutation that has been selected for in many popular dog breeds e.g. the Bulldog, Pug, and French Bulldog. A chronic, debilitating respiratory syndrome, whereby soft tissue blocks the airways, predominantly affects dogs with this conformation, and thus is labelled Brachycephalic Obstructive Airway Syndrome (BOAS). Despite the name of the syndrome, scientific evidence quantitatively linking brachycephaly with BOAS is lacking, but it could aid efforts to select for healthier conformations. Here we show, in (1) an exploratory study of 700 dogs of diverse breeds and conformations, and (2) a confirmatory study of 154 brachycephalic dogs, that BOAS risk increases sharply in a non-linear manner as relative muzzle length shortens. BOAS only occurred in dogs whose muzzles comprised less than half their cranial lengths. Thicker neck girths also increased BOAS risk in both populations: a risk factor for human sleep apnoea and not previously realised in dogs; and obesity was found to further increase BOAS risk. This study provides evidence that breeding for brachycephaly leads to an increased risk of BOAS in dogs, with risk increasing as the morphology becomes more exaggerated. As such, dog breeders and buyers should be aware of this risk when selecting dogs, and breeding organisations should actively discourage exaggeration of this high-risk conformation in breed standards and the show ring

Repetitive Brain Injury of Juvenile Mice Impairs Environmental Enrichment-Induced Modulation of REM Sleep in Adulthood

Traumatic brain injuries (TBIs) are a common and costly ongoing public health concern. Injuries that occur during childhood development can have particularly profound and long-lasting effects. One common consequence and potential mediator of negative outcomes of TBI is sleep disruption which occurs in a substantial proportion of TBI patients. These individuals report greater incidences of insomnia and sleep fragmentation combined with a greater overall sleep requirement meaning that many patients are chronically sleep-deprived. We sought to develop an animal model of developmental TBI-induced sleep dysfunction. Specifically, we tested the hypothesis that early (postnatal day 21), repeated closed head injuries in Swiss-Webster mice, would impair basal and homeostatic sleep responses in adulthood. Further, we asked whether environmental enrichment (EE), a manipulation that improves functional recovery following TBI and has been shown to alter sleep physiology, would prevent TBI-induced sleep dysfunction and alter sleep-modulatory peptide expression. In contrast to our hypothesis, the mild, repeated head injury that we used did not significantly alter basal or homeostatic sleep responses in mice housed in standard laboratory conditions. Sham-injured mice housed in enriched environments exhibited enhanced rapid eye movement (REM) sleep and expression of the REM-promoting peptide pro-melanin-concentrating hormone, an effect that was not apparent in TBI mice housed in enriched environments. Thus, TBI blocked the REM-enhancing effects of EE. This work has important implications for the management and rehabilitation of the TBI patient population

miR-155 deletion modulates lipopolysaccharide-induced sleep in female mice

Immune signaling is known to regulate sleep. miR-155 is a microRNA that regulates immune responses. We hypothesized that miR-155 would alter sleep regulation. Thus, we investigated the potential effects of miR-155 deletion on sleep-wake behavior in adult female homozygous miR-155 knockout (miR-155(KO)) mice and littermate controls (WT). Mice were implanted with biotelemetry units and EEG/EMG biopotentials were recorded continuously for three baseline days. miR-155(KO) mice had decreased bouts of NREM and REM sleep compared with WT mice, but no differences were observed in the length of sleep bouts or total time spent in sleep-wake states. Locomotor activity and subcutaneous temperature did not differ between WT and miR-155(KO) mice. Following baseline recordings, mice were sleep-deprived during the first six hours of the rest phase (light phase; ZT 0-6) followed by an 18 h recovery period. There were no differences between groups in sleep rebound (% sleep and NREM delta power) after sleep deprivation. Following recovery from sleep deprivation, mice were challenged with a somnogen (viz., lipopolysaccharide (LPS)) one hour prior to the initiation of the dark (active) phase. Biopotentials were continuously recorded for the following 24 h, and miR-155(KO) mice displayed increased wakefulness and decreased NREM sleep during the dark phase following LPS injection. Additionally, miR-155(KO) mice had reduced EEG slow-wave responses (0.5-4 Hz) compared to WT mice. Together, our findings indicate that miR-155 deletion attenuates the somnogenic and EEG delta-enhancing effects of LPS. Abbreviations: ANOVA: analysis of variance; EEG: electroencephalogram; EMG: electromyogram; h: hour; IL-1: interleukin-1; IL-6: interleukin-6; IP: intra-peritoneal; LPS: lipopolysaccharide; miR/miRNA: microRNA; miR-155(KO): miR-155 knockout; NREM: non-rapid eye movement; REM: rapid eye movement; TNF: tumor necrosis factor; SWS: slow-wave sleep; WT: wild-type

GENERALIZABLE OSA CLINICAL SUBGROUPS IN AN INTERNATIONAL SLEEP CENTER POPULATION

Univ Penn, Ctr Sleep & Circadian Neurobiol, Philadelphia, PA 19104 USAUniv Penn, Sch Nursing, Philadelphia, PA 19104 USAUniv Fed Sao Paulo, Dept Psychobiol, Sao Paulo, BrazilChang Gung Mem Hosp, Div Pulm Crit Care & Sleep Med, Taoyuan, TaiwanUniv Sydney, Royal North Shore Hosp, Sydney, NSW, AustraliaUniv Sydney, Charles Perkins Ctr, Northern Clin Sch, Sydney, NSW, AustraliaOhio State Univ, Wexner Med Ctr, Div Pulm Allergy Crit Care & Sleep Med, Columbus, OH 43210 USASir Charles Gairdner Hosp, West Australian Sleep Disorders Res Inst, Dept Pulm Physiol & Sleep Med, Perth, WA, AustraliaCharite, Interdisciplinary Ctr Sleep Med, Berlin, GermanyAgaples Bethesda Krankenhaus Wuppertal, Dept Pulm Med, Wuppertal, GermanyKorea Univ, Med Ctr, Ansan Hosp, Pulm Crit Care & Sleep Disorder Ctr, Seoul, South KoreaLandspitali Univ Hosp, Dept Resp Med & Sleep, Reykjavik, IcelandUniv Fed Sao Paulo, Dept Psychobiol, Sao Paulo, BrazilWeb of Scienc

ANTHROPOMETRIC DIFFERENCES IN OSA ACROSS FOUR ETHNIC GROUPS IN OSA ACROSS FOUR ETHNIC GROUPS

Univ Sydney, Sydney, NSW, AustraliaUniv Penn, Ctr Sleep & Circadian Neurobiol, Philadelphia, PA 19104 USAUniv Fed Sao Paulo, Psychobiol, Sao Paulo, BrazilChang Gung Mem Hosp, Sleep Ctr, Dept Pulm & Crit Care Med, Taipei, TaiwanLandspitali Univ Hosp, Dept Resp Med & Sleep, Reykjavik, IcelandOhio State Univ, Wexner Med Ctr, Div Pulm Crit Care & Sleep Med, Columbus, OH 43210 USAUniv Penn, Perelman Sch Med, Div Sleep Med, Philadelphia, PA 19104 USAChildrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USASir Charles Gairdner Hosp, West Australian Sleep Disorders Res Inst, Dept Pulm Physiol & Sleep Med, Perth, WA, AustraliaCharite, Interdisciplinary Ctr Sleep Med, Berlin, GermanyUniv Sydney, Charles Perkins Ctr, Sydney, NSW, AustraliaUniv Fed Sao Paulo, Psychobiol, Sao Paulo, BrazilWeb of Scienc

A Role for Hypocretin/Orexin in Metabolic and Sleep Abnormalities in a Mouse Model of Non-metastatic Breast Cancer

We investigated relationships among immune, metabolic, and sleep abnormalities in mice with non-metastatic mammary cancer. Tumor-bearing mice displayed interleukin-6 (IL-6)-mediated peripheral inflammation, coincident with altered hepatic glucose processing and sleep. Tumor-bearing mice were hyperphagic, had reduced serum leptin concentrations, and enhanced sensitivity to exogenous ghrelin. We tested whether these phenotypes were driven by inflammation using neutralizing monoclonal antibodies against IL-6; despite the reduction in IL-6 signaling, metabolic and sleep abnormalities persisted. We next investigated neural populations coupling metabolism and sleep, and observed altered activity within lateral-hypothalamic hypocretin/orexin (HO) neurons. We used a dual HO-receptor antagonist to test whether increased HO signaling was causing metabolic abnormalities. This approach rescued metabolic abnormalities and enhanced sleep quality in tumor-bearing mice. Peripheral sympathetic denervation prevented tumor-induced increases in serum glucose. Our results link metabolic and sleep abnormalities via the HO system, and provide evidence that central neuromodulators contribute to tumor-induced changes in metabolism