See details at www.jeremyborniger.com
Doctor of Philosophy, Ohio State University (2017)
Bachelor of Arts, Indiana University (2011)
miR-155 deletion modulates lipopolysaccharide-induced sleep in female mice
2019; 36 (2): 188–202
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-155KO) mice and littermate controls (WT). Mice were implanted with biotelemetry units and EEG/EMG biopotentials were recorded continuously for three baseline days. miR-155KO 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-155KO 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 δ 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-155KO mice displayed increased wakefulness and decreased NREM sleep during the dark phase following LPS injection. Additionally, miR-155KO 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-155KO: miR-155 knockout; NREM: non-rapid eye movement; REM: rapid eye movement; TNF: tumor necrosis factor; SWS: slow-wave sleep; WT: wild-type.
View details for DOI 10.1080/07420528.2018.1525617
View details for Web of Science ID 000456977400004
View details for PubMedID 30299169
Hypocretin as a Hub for Arousal and Motivation
FRONTIERS IN NEUROLOGY
2018; 9: 413
The lateral hypothalamus is comprised of a heterogeneous mix of neurons that serve to integrate and regulate sleep, feeding, stress, energy balance, reward, and motivated behavior. Within these populations, the hypocretin/orexin neurons are among the most well studied. Here, we provide an overview on how these neurons act as a central hub integrating sensory and physiological information to tune arousal and motivated behavior accordingly. We give special attention to their role in sleep-wake states and conditions of hyper-arousal, as is the case with stress-induced anxiety. We further discuss their roles in feeding, drug-seeking, and sexual behavior, which are all dependent on the motivational state of the animal. We further emphasize the application of powerful techniques, such as optogenetics, chemogenetics, and fiber photometry, to delineate the role these neurons play in lateral hypothalamic functions.
View details for PubMedID 29928253
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.
View details for DOI 10.1016/j.cmet.2018.04.021
View details for PubMedID 29805100
Repetitive Brain Injury of Juvenile Mice Impairs Environmental Enrichment-Induced Modulation of REM Sleep in Adulthood
2018; 375: 74–83
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.
View details for DOI 10.1016/j.neuroscience.2018.01.064
View details for Web of Science ID 000426996600007
View details for PubMedID 29432885
The Heart ' s rhythm "n' blues: Sex differences in circadian variation patterns of vagal activity vary by depressive symptoms in predominantly healthy employees
2018; 35 (7): 896–909
Successful regulation of emotional states is positively associated to mental health, while difficulties in regulating emotions are negatively associated to overall mental health and in particular associated with anxiety or depression symptoms. A key structure associated to socio-emotional regulatory processes is the central autonomic network. Activity in this structure is associated to vagal activity can be indexed noninvasively and simply by measures of peripheral cardiac autonomic modulations such as heart rate variability. Vagal activity exhibits a circadian variation pattern, with a maximum during nighttime. Depression is known to affect chronobiology. Also, depressive symptoms are known to be associated with decreased resting state vagal activity, but studies investigating the association between circadian variation pattern of vagal activity and depressive symptoms are scarce. We aim to examine these patterns in association to symptom severity of depression using chronobiologic methods.Data from the Manheim Industrial Cohort Studies (MICS) were used. A total of 3,030 predominantly healthy working adults underwent, among others, ambulatory 24-h hear rate-recordings, detailed health examination and online questionnaires and were available for this analysis. The root mean sum of successive differences (RMSSD) was used as an indicator of vagally mediated heart rate variability. Three individual-level cosine function parameters (MESOR, amplitude, acrophase) were estimated to quantify circadian variation pattern. Multivariate linear regression models including important covariates such as age, sex, and lifestyle factors as well as an interaction effect of sex with depressive symptoms were used to estimate the association of circadian variation pattern of vagal activity with depressive symptoms simultaneously.The analysis sample consisted of 20.2% females and an average age 41 with standard deviation of 11 years. Nonparametric bivariate analysis revealed significant MESOR and amplitude differences between the 90th percentile split, but not on acrophase. Multivariate linear regression models estimated depressive symptoms to be negatively associated with the 24h mean (MESOR) and oscillation amplitude in men but positively associated in women. This pattern of findings indicates a blunted day-night rhythm of vagal activity in men with greater depressive symptoms as well as a moderation effect of sex in the association of CVP and depressive symptoms.This is the first study investigating circadian variation pattern by mild depressive symptoms in a large, rather healthy occupational sample. Depressive symptoms were associated with decreased circadian variation pattern of vagal activity in men but with increased circadian variation pattern in women. The possible underlying mechanism(s) are discussed using the neurovisceral integration model. These findings may have implications for the knowledge on etiology, diagnosis, course, and treatment of depressive symptoms and thus may be of significant public health relevance.
View details for PubMedID 29543518