Sleep Measured by Subjective Reports

A notable concern with using PSG is the cost and potential burden to the subject and the investigator (Reichert et al. 2003). Furthermore, physiological sleep measures do not capture the perception of the sleep by the individual, which in many instances is as crucial as the objective data (R. Bootzin, pers. commun.). Therefore, subjective reports can be useful in detecting sleep disturbances, particularly during pregnancy. Unfortunately, studies of sleep during pregnancy use various subjective...

Age Related Changes in Sleep and Relation to Altered Immunity

A focus of our own interest, as indeed for a number of other groups, has been the age-related changes which occur in sleep performance, and their interrelationship with simultaneous changes known to occur with immune functioning with age. Human sleep in old age is characterized by a number of changes, including sleep fragmentation and reductions in sleep efficiency and amounts of visually scored slow-wave and REM sleep, as well as amplitude of the diurnal sleep wake rhythm. While acknowledging...

TBI and Sleep

Close to 25 of patients with TBI develop some form of psychopathological or psychiatric disorder, including posttraumatic stress disorder, physical, cognitive-memory, and behavioral complications, such as sleep disturbances (Frieboes et al., 1999). Insomnia is a prevalent condition after TBI, although most reports rely on self-administered questionnaires rather than laboratory data (Steele, Rajaratnam, Redman, and Ponsford 2005). Sleep disruption is a defining feature of anxiety and is...

Genetic Variation in Sleep Under Normal Conditions and during Inflammatory Disease

Several sleep and circadian disorders, including narcolepsy, advanced sleep phase syndrome (ASPS), and fatal familial insomnia (FFI), have known genetic determinants. For example, canine narcolepsy is transmitted as a single autosomal recessive trait with full penetrance (Mignot et al. 1991). The critical genetic determinant for canine narcolepsy is a mutation in the hypocretin receptor gene HCRTR2 (Lin et al. 1999). This finding spurred studies that revealed low levels of hypocretin-1 in the...

References

Ader, R. (1996) Historical perspectives on psychoneuroimmunology. In H. Friedman, T.W. Klein, and A.L. Friedman (Eds.), Psychoneuroimmunology, Stress, and Infection. CRC Press, Boca Raton, pp. 1-24. Ader, R., and Cohen, N. (1975) Behaviorally conditioned immunosuppression. Psychosom Med 37, 333-340. Aguila, M.C., Rodriguez, A.M., Aguila-Mansila, H.N., and Lee, W.T. (1996) Somatostatin antisense oligodeoxynucleotide-mediated stimulation of lymphocyte proliferation in culture. Endocrinology 137,...

Epidemiology and Clinical Features

Narcolepsy is a disabling sleep disorder characterized by severe excessive daytime sleepiness and abnormal rapid eye movement (REM) sleep manifestations including cataplexy, sleep paralysis, hypnagogic hallucinations, and sleep onset REM periods (American Academy of Sleep Medicine 2005 Dauvilliers, Billiard, and Montplaisir 2003b Scammell 2003). Recent advances in pathophysiology demonstrated that narcolepsy is caused by the loss of hypothalamic neurons producing hypocretin (Mignot et al. 2002...

Neuroendocrine Hormone Release by Cells of the Immune System

There is now substantial evidence that cells of the immune system produce neuroendocrine hormones. This was first established for ACTH and subsequently for TSH, GH, PRL, LH, FSH and the hypothalamic hormones SOM, CRH, GHRH, and LHRH (Weigent and Blalock 1995). The evidence supports the idea that neuroendocrine peptides and neurotransmitters, endogenous to the immune system, are used for both intraimmune system regulation, as well as for bidirectional communication between the immune and...

Immune Function in Sleep Disorders

Insomnia and obstructive sleep apnea are the most prevalent sleep disorders in the general population (Ancoli-Israel 1993). Such disturbances result in major alterations in the immune system and may be mediated by the augmented activity of the HPA axis and or sympathetic nervous system, as we will soon describe. There is evidence of the association of insomnia and elevated HPA axis activity. Primary insomnia patients connect the onset of the disorder to some stressful event. Chronic...

Insomnia in Aging Influence on Immunity

Normal healthy aging is associated with increasing sleep fragmentation, increasingly light sleep (stages 1 and 2), and less slow wave sleep (SWS, stages 3 and 4) (Benca, Obermeyer, Thisted, and Gillin 1992 Ehlers and Kupfer 1997 Van Cauter, Leproult, and Plat 2000). These changes are thought to contribute to daytime fatigue, depression, and impairments in health functioning in older adults. Such changes in sleep parameters may explain why self reported poor sleep is one of the most common...

Genetic Variation in the Inflammatory Response

Inflammation drives the development or severity of a large number of diseases (e.g., atherosclerosis, asthma, ulcerative colitis, postmenopausal osteoporosis, sleep disorders). Variation in genes that encode proteins regulating inflammation may underlie a large proportion of interindividual variation in susceptibility to numerous diseases. Furthermore, variation in the production or function of cytokines can cause variation in inflammatory responses that in turn influences the progression of...

PRL Molecular Aspects

After the processing of a 28 residue signal peptide, the mature human PRL molecule is secreted as a polypeptide with 199 amino acid residues, whereas mouse PRL is two residues shorter (Cooke 1989). In both species, six cysteines form three intramolecular disulfide bridges. The molecular weight of human PRL is approximately 23 kDa, but a 26-kDa glycosylated form is also produced. PRL circulates in blood as monomers of 23 to 26 kDa (Lewis, Sigh, Sinha, and Vanderlaan 1985). Larger macroprolactins...

OSAS Neuroimmunology

The links between immune system and sleep were first identified in the 1970s, when a sleep-inducing factor was isolated and chemically characterized from human urine Factor S, a muramyl peptide derived from bacterial peptoglycan. Subsequently muramyl dipeptide and Factor S-related peptidoglycans were all shown to induce the key immunoregulatory cytokine. Then interleukin (IL)-ip was shown to be a potent somnogen, as well as a potent pyrogen. In fact, IL-ip is one of the most neurologically...

Norepinephrine Release and Clearance

What is the source of elevated NE levels in OSA Venous and arterial NE levels reflect not only release, but metabolic degradation reuptake, diffusion, and regional and local circulation. Catecholamines are cleared by reuptake into nerves (referred to as uptake 1) and by uptake into nonneuronal tissue (referred to as uptake 2). NE is cleared by uptake 1 more than other catecholamines. Tracer amounts of radiolabeled NE can be used to measure the release rate and the clearance rate of NE, which...

Sleep Measured by Inlab Polysomnography

There is agreement within the professional sleep community (American Sleep Disorders Association 1997) of a pregnancy-associated sleep disorder, however much of the data are inconsistent and contradictory. The discrepancies stem primarily from changes in technology and in the understanding of sleep over the past several decades. Early studies were able to suggest only crude estimations of sleep changes due to limitations of the EEG recording equipment used (Branchey and Petre-Quadens 1968...

Neuroendocrine Hormone Influence on the Immune System

The immune system, in addition to autonomic nervous activity, is influenced by hormones released by the neuroendocrine system (Table 1.3 see also Brooks (1990), Carr (1992), Clevenger, Sillman, and Prystowsky (1990), Clevenger, Sillman, Hanley-Hyde, and Prystowsky (1992), Foster, Mandak, Kromer, and Rot (1992), Jain et al. (1991), Johnson, Farrar, and Torres (1982a), Johnson, Smith, Torres, and Blalock (1982b), Johnson, Torres, Smith, Dion, and Blalock (1984), Kelley (1989), Kruger, Smith,...

TBI and the Neuroendocrine System

Tbi And Sleep

Trauma to the hypothalamus frequently occurs in severe head injuries (Crompton 1971 Rudy 1980). The hypothalamus can be injured as a result of direct or indirect damage, small hemorrhages, or ischemia (cf. Lighthall, Gochgarian, and Pinderski 1990). Sudden head movement can shear blood vessels supplying this part of the brain (Mitchell, Steffenson, and Davenport 1997). Regulation of the neuroendocrine systems involves numerous pathways and centers, including afferent neural pathways, the...

Relationship of Infection to Altered Sleep Behavior

Sleep has been proposed as an innate host defense, exerting effects on both specific and nonspecific immunity. One of the most seminal studies dealing with the effects of sleep on immune potential was that from Brown's group showing that depriving influenza virus-immune mice of sleep for 7 h following total respiratory tract viral challenge abrogated antiviral immunity within the lungs and lowered the level of anti-influenza antibody in lung homogenates (Brown 1989). In immune mice...

Other Cytokines

Although there is good evidence to support a role for TNF and IL-1P in the impact of infections on sleep, the role of other cytokines is more ambiguous. This might reflect either the lack of a direct role or problems with experimental design. IL-2, IL-5, IL-18, INF-a, and INF-y usually increase the duration of sleep, whereas IL-4, IL-10, and IL-13 usually inhibit spontaneous sleep. The effect of IL-6 is less conclusive. In rats, it has been reported to be either somnogenic or to have no effect...

Cytokine Balance and Antidepressants

18.8.1 Effect of Multitarget Drugs (e.g., Monoamine Transporter Blockers) More recently, a number of studies focused on the pro and anti-inflammatory cytokine balance in major depressive disorders. A dysregulation within the cytokine balance could induce depressive symptoms due to lower levels of anti-inflammatory cytokines and higher levels of proinflammatory cytokines. Anti-inflammatory cytokines or cytokine receptors are known to evoke an antiinflammatory state both on their own (IL-10,...

Chronic Fatigue Syndrome

Chronic fatigue syndrome (CFS) is a condition of unknown etiology that is diagnosed based on patient report of an array of clinical symptoms, generally in the absence of an organic or inciting etiology. Key diagnostic features are severe fatigue of more than 6 months duration and a subset of other symptoms that can include impairments of memory or the ability to concentrate, tender lymph nodes, myalgia, arthralgia, headache, cognitive disturbances, low-grade fever, disturbed sleep, sore throat,...

Neurotransmitter Release by Cells of the Immune System

Lymphocytes have also been suggested to be important sites of synthesis and action of acetylcholine and catecholamines since they contain both the enzymes necessary for biosynthesis of epinephrine and acetylcholine as well as the relevant receptor system (Bergquist, Tarkowski, Ekman, and Ewing. 1994 Tayebati, El-Assouad, Ricci, and Amenta 2002 Warthan et al. 2002). The synthesis of catecholamines was shown to increase after mitogen treatment of rat lymphocytes obtained from spleen, thymus, and...

Allostatic Response and Allostatic Intervention Relevance to Oral Biology and Medicine

The nineteenth-century French physiologist, Claude Bernard (1813-1878) proposed that preservation of the internal milieu (le milieu int rieur, 1856) is a fundamental process of physiological regulation. The phrase homeostasis was coined. However, the concept of the benefits reaped by a state of physiological balance goes back millennia and across cultures, medical traditions and civilizations. In Western civilization, we need to go beyond the classic Roman view of a healthy mind in a healthy...

The Immune System Shows Circadian Organization

Light and daily rhythms have a profound influence on immune function. Many studies have described circadian variations of different immune parameters such as lymphocyte proliferation, antigen presentation, and cytokine gene expression. The number of lymphocytes and monocytes in the human blood reach maximal values during the night and are lowest after waking. Natural killer (NK) cells, by contrast, reach their highest level in the afternoon, with a normal decrease in number and activity around...

PRL and Sleep Regulation

In 1986 Michel Jouvet showed that the systemic administration of PRL enhances the total time of REMS in cats (Jouvet et al. 1986). Studies in hypoprolactinemic rats showed that REMS duration was decreased, also circadian rhythm of REMS disappeared, while that of nonrapid eye movements sleep (NREMS) remains unchanged (Valatx and Jouvet 1988). Figure 5.2. Representation of PRL and its receptor (PRLR) signaling pathways. Long and short isoforms of the PRLR are represented. PRLR activates STAT1,...

Cytokines in OSA

Akin to neurotransmitters of the nervous system (such as NE), cytokines are key mediators of vast immune and neuroimmune interactions. There are many features of OSA that argue for the importance of studying cytokines, including neuroimmune interactions, mood changes (such as fatigue and depression), and behaviors that directly affect the course of the disorder (such as caffeine consumption, smoking, diet, and difficulties with adherence to treatment). Before reviewing studies of OSA and...

Interactions Between the Biological Clock and the Sleep Switch

The suprachiasmatic nucleus (SCN) in the anterior hypothalamus is also referred to as the biological clock, since it acts as a major pacemaker in the mammalian brain to drive various circadian rhythms. One important feature of circadian rhythmicity is the sleep-wake cycle, which is greatly influenced by signals originating in the SCN. In spite of the close relation between the circadian timing and sleep-wake regulating systems, their physiological, anatomical, and possibly humoral,...

Regulation of Cytokine Balance by Monoamines in Healthy and in Depressed States

The major source of cytokine production is the peripheral immune system, although cytokines are also produced in the CNS. It is now well established that immune activation triggers the sympathetic nervous system (SNS) to release its neurotransmitters NE, epinephrine, and dopamine (Besedovsky, del Rey, Sorkin, and Dinarello 1986 Akiyoshi, Shimizu, and Saito 1990 Shimizu, Hori, and Nakane 1994). The sympathetic nervous system innervates immune organs and, when activated, releases its signaling...

Sleep Disturbances in Diseased States Associated with Altered Cytokine Profile

Although it is well recognized that infection is commonly associated with somnolence and fatigue, the mechanism of such behaviors has only been investigated within the last 10 years. For instance, it is now believed that muramyl peptide, a common microbial product, and bacterial endotoxin (LPS) stimulate the release of proinflammatory cytokines that interact with specific neurohormones and neurotransmitters in the brain to produce somnogenic activity (Krueger and Majde 1994). Some human studies...

Introduction

Sleep is a necessary behavior for physiological allostasis that is common to all vertebrates. Allostasis refers to the set of intertwined neuroendocrine-immune processes of bodily adaptation to stressful challenges during the wake cycle. The summative effects of these challenges, the allostatic load, signifies the total cost of wear and tear to the body. A finely regulated neuroimmunology of the sleep component of the circadian patterns is critical to the physiological repair mechanism required...

Nasal Continuous Positive Airway Pressure

A common and effective treatment for OSA is nasal continuous positive airway pressure (CPAP). When air is pumped at positive pressure through a facemask, the patient's airway is kept open, reducing the number of apneas (respiratory suspensions) and hypopneas (reductions in airflow and oxygenation during sleep) With CPAP, the majority of patients are able to get their first good night's sleep in years. We have conducted several therapeutic treatment studies using CPAP to see if the positive...

Effects of Inflammatory Molecules on the SCN and Sleep Switch Structures

Certain molecules originally defined on the basis of their role in inflammation display activities in the sleep-wakefulness-promoting structures, namely histamine as well as interleukin (IL)-ip and tumor necrosis factor (TNF)-a. During peripheral inflammation, the biogenic amine histamine is released from mast cells and is a major mediator of vasodilation and permeability, but in the brain it acts mainly as an excitatory neurotransmitter. Histamine is produced by neurons located in the TMN,...

Melatonin Role and Circadian Rhythms in Children with OSAS

Melatonin is produced by pineal gland. Light inhibits its secretion. Hence, a rhythmical secretion pattern is seen in all species, including humans. In humans, the highest melatonin levels are found in 2- to 5-year-old children from that age, secretion decrease progressively (Waldhauser, Weiszenbacher, and Tatzer 1988). It has long been known that melatonin has sleep-promoting properties and regulates the sleep-wake cycle. Melatonin has a strong circadian rhythm with high values during the...

Cytokines and Sleep

As will be discussed in more detail below, sleep is affected by infection, a primary driving force for nonspecific inflammation and cytokine production. It should come as no surprise therefore that a number of groups have examined in detail the evidence for an interaction between modulation of cytokine production and altered sleep behavior. This is reviewed in more detail elsewhere in this volume, but some brief mention is necessary before further discussion of altered sleep in disease. As a...

What Are the Links Between Immune Brain Interfaces and Sleep Neurocircuitry

Pedunculopontine Reticular

In order for peripherally generated immune signals to influence sleep, immuno-sensory interfaces must connect with the arousal-related neurocircuitry outlined above. The following describes immune-responsive brain regions that likely relay immune-related information to the brain regions that control arousal and the pathways by which they target these regions. Figure 6.1. Schematic representations (modified after Saper et al. 2005) of key components of the ascending reticular arousal system...

Mucositis A Case of Allostatic Load 231 Oral Mucositis

An important example of Type 2 allostasis in oral biology and medicine, which could benefit from fractal analysis, is the clinical condition of oropharyngeal mucositis OM, Fig. 2.2 . The term mucositis and stomatitis are often used interchangeably, but OM specifically pertains to pharyngeal-esophago-gastro-intestinal inflammation, that manifests as red, burn-like sore or ulcerations throughout the mouth. Stomatitis is an inflammation of the oral tissues proper, which can present with or without...