Role of vasoactive intestinal peptide in the light input to the circadian system.

The neuropeptide vasoactive intestinal peptide (VIP) is expressed at high levels in a subset of neurons in the ventral region of the suprachiasmatic nucleus (SCN). While VIP is known to be important for the synchronization of the SCN network, the role of VIP in photic regulation of the circadian system has received less attention. In the present study, we found that the light-evoked increase in electrical activity in vivo was unaltered by the loss of VIP. In the absence of VIP, the ventral SCN still exhibited N-methyl-d-aspartate-evoked responses in a brain slice preparation, although the absolute levels of neural activity before and after treatment were significantly reduced. Next, we used calcium imaging techniques to determine if the loss of VIP altered the calcium influx due to retinohypothalamic tract stimulation. The magnitude of the evoked calcium influx was not reduced in the ventral SCN, but did decline in the dorsal SCN regions. We examined the time course of the photic induction of Period1 in the SCN using in situ hybridization in VIP-mutant mice. We found that the initial induction of Period1 was not reduced by the loss of this signaling peptide. However, the sustained increase in Period1 expression (after 30 min) was significantly reduced. Similar results were found by measuring the light induction of cFOS in the SCN. These findings suggest that VIP is critical for longer-term changes within the SCN circuit, but does not play a role in the acute light response.

Perceptions of interprofessional education and practice within a complementary and alternative medicine institution.

A survey of the constituents of a complementary and alternative medicine (CAM) institution was conducted to identify perceptions of interprofessional education (IPE) and practice (IPP). A 22 question survey was developed and administered to: chiropractic students, acupuncture and oriental medicine students, faculty and alumni of both professions, staff and administrators. The majority of the 321 respondents demonstrated positive perceptions of IPE and IPP, however many reported a lack of understanding of the distinct roles of select healthcare professions. The study also suggested that the campus community is not homogenous in its understanding of CAM or allopathic professions, or is it homogenous in its understanding of IPE and IPP. While the overall positive attitudes toward IPE and IPP imply a willingness to improve collaboration between these groups, the lack of understanding of profession-specific roles must be addressed to support effective implementation of IPE.

Circadian regulation of a-type potassium currents in the suprachiasmatic nucleus.

In mammals, the precise circadian timing of many biological processes depends on the generation of oscillations in neural activity of pacemaker cells in the suprachiasmatic nucleus (SCN) of the hypothalamus. Understanding the ionic mechanisms underlying these rhythms is an important goal of research in chronobiology. Previous work has shown that SCN neurons express A-type potassium currents (IAs), but little is known about the properties of this current in the SCN. We sought to characterize some of these properties, including the identities of IA channel subunits found in the SCN and the circadian regulation of IA itself. In this study, we were able to detect significant hybridization for Shal-related family members 1 and 2 (Kv4.1 and 4.2) within the SCN. In addition, we used Western blot to show that the Kv4.1 and 4.2 proteins are expressed in SCN tissue. We further show that the magnitude of the IA current exhibits a diurnal rhythm that peaks during the day in the dorsal region of the mouse SCN. This rhythm seems to be driven by a subset of SCN neurons with a larger peak current and a longer decay constant. Importantly, this rhythm in neurons in the dorsal SCN continues in constant darkness, providing an important demonstration of the circadian regulation of an intrinsic voltage-gated current in mammalian cells. We conclude that the anatomical expression, biophysical properties, and pharmacological profiles measured are all consistent with the SCN IA current being generated by Kv4 channels. Additionally, these data suggest a role for IA in the regulation of spontaneous action potential firing during the transitions between day/night and in the integration of synaptic inputs to SCN neurons throughout the daily cycle.

The role of the neuropeptides PACAP and VIP in the photic regulation of gene expression in the suprachiasmatic nucleus.

Previously, we have shown that mice deficient in either vasoactive intestinal peptide (VIP) or pituitary adenylate cyclase-activating polypeptide (PACAP) exhibit specific deficits in the behavioral response of their circadian system to light. In this study, we investigated how the photic regulation of the molecular clock within the suprachiasmatic nucleus (SCN) is altered by the loss of these closely-related peptides. During the subjective night, the magnitude of the light-induction of FOS and phosphorylated mitogen-activated protein kinase (p-MAPK) immunoreactive cells within the SCN was significantly reduced in both VIP- and PACAP-deficient mice when compared with wild-type mice. The photic induction of the clock gene Period1 (Per1) in the SCN was reduced in the VIP- but not in the PACAP-deficient mice. Baselines levels of FOS, p-MAPK or Per1 in the night were not altered by the loss of these peptides. In contrast, during the subjective day, light exposure increased the levels of FOS, p-MAPK and Per1 in the SCN of VIP-deficient mice, but not in the other genotypes. During this phase, baseline levels of these markers were reduced in the VIP-deficient mice compared with untreated controls. Finally, the loss of either neuropeptide reduced the magnitude of the light-evoked increase in Per1 levels in the adrenals in the subjective night without any change in baseline levels. In summary, our results indicate that both VIP and PACAP regulate the responsiveness of cells within the SCN to the effects of light. Furthermore, VIP, but not PACAP, is required for the appropriate temporal gating of light-induced gene expression within the SCN.

Perceived stress and fatigue among students in a doctor of chiropractic training program.

OBJECTIVE: High levels of stress and fatigue are associated with decreased academic success, well-being, and quality of life. The objective of this research was to quantify levels of perceived stress and fatigue among chiropractic students to identify sources of and student coping mechanisms for perceived stress and fatigue and to identify the relationship between students' perceived stress and fatigue. METHODS: A survey comprised of the Perceived Stress Scale, the Undergraduate Sources of Stress Survey, and the Piper Fatigue Scale was administered to chiropractic students in their 2nd, 5th, and 8th trimesters of doctoral study. Data were analyzed by descriptive statistics, 1-way analysis of variance, and linear correlation tests. RESULTS: Students reported having moderate to high levels of stress and fatigue, with higher levels of stress and fatigue seen in women than in men. A nonsignificant difference among stress scores and a significant difference among fatigue scores were observed based on program term. Levels of stress predicted levels of fatigue, and stress was strongly correlated with psychological health, relationships with family members, mood, and need for learning accommodations. Fatigue was strongly correlated with psychological health, academic demands, and conflicts between studies and other activities. CONCLUSION: There are differences in the reporting of perceived stress and fatigue levels in this chiropractic student population based on gender. The correlation between fatigue and stress also suggests that measures that may alleviate one may likely affect the other.

Bow hunter's syndrome in a patient with vertebral artery atresia, an arcuate foramen, and unilateral deafness: a case report.

Bow hunter's syndrome (BHS) is a rare cause of vertebrobasilar insufficiency that occurs when the vertebral artery (VA) is occluded on rotation of the head and neck. This dynamic occlusion of the VA can occur anywhere along its course after it arises from the subclavian artery. Although most cases are associated with compression by osteophytes, cervical spondylosis, or lateral disc herniation, BHS has a highly variable clinical course that depends on the patient's specific anatomy. Therefore, it may be important for clinicians to be aware of anatomical variants that predispose individuals to BHS. Here, we report on a patient with BHS who was found to have two uncommon anatomical anomalies: an atretic right VA and a left-sided arcuate foramen.

Gonadal- and sex-chromosome-dependent sex differences in the circadian system.

Compelling reasons to study the role of sex in the circadian system include the higher rates of sleep disorders in women than in men and evidence that sex steroids modulate circadian control of locomotor activity. To address the issue of sex differences in the circadian system, we examined daily and circadian rhythms in wheel-running activity, electrical activity within the suprachiasmatic nucleus, and PER2::LUC-driven bioluminescence of gonadally-intact adult male and female C57BL/6J mice. We observed greater precision of activity onset in 12-hour light, 12-hour dark cycle for male mice, longer activity duration in 24 hours of constant darkness for female mice, and phase-delayed PER2::LUC bioluminescence rhythm in female pituitary and liver. Next, in order to investigate whether sex differences in behavior are sex chromosome or gonadal sex dependent, we used the 4 core genotypes (FCG) mouse model, in which sex chromosome complement is independent of gonadal phenotype. Gonadal males had more androgen receptor expression in the suprachiasmatic nucleus and behaviorally reduced photic phase shift response compared with gonadal female FCG mice. Removal of circulating gonadal hormones in adults, to test activational vs organizational effects of sex revealed that XX animals have longer activity duration than XY animals regardless of gonadal phenotype. Additionally, we observed that the activational effects of gonadal hormones were more important for regulating activity levels in gonadal male mice than in gonadal female FCG mice. Taken together, sex differences in the circadian rhythms of activity, neuronal physiology, and gene expression were subtle but provide important clues for understanding the pathophysiology of the circadian system.

Jet lag syndrome: circadian organization, pathophysiology, and management strategies.

The circadian system regulates the cyclical occurrence of wakefulness and sleep through a series of oscillatory networks that comprise two different theoretical processes. The suprachiasmatic nucleus (SCN) of the hypothalamus contains the master oscillatory network necessary for coordinating these daily rhythms, and in addition to its ability to robustly generate rhythms, it can also synchronize to environmental light cues. During jet lag, abrupt shifts in the environmental light-dark cycle temporarily desynchronize the SCN and downstream oscillatory networks from each other, resulting in increased sleepiness and impaired daytime functioning. Polysomnographic data show that not only does jet lag result in changes of sleep-wake timing, but also in different aspects of sleep architecture. This type of circadian misalignment can further lead to a cluster of symptoms including major metabolic, cardiovascular, psychiatric, and neurological impairments. There are a number of treatment options for jet lag involving bright light exposure, melatonin, and use of hypnotics, but their efficacy greatly depends on their time of use, the length of time in the new time zone, and the specific circadian disturbance involved. The aim of this review is to provide mechanistic links between the fields of sleep and circadian rhythms to understand the biological basis of jet lag and to apply this information to clinical management strategies.

Period gene expression in the diurnal degu (Octodon degus) differs from the nocturnal laboratory rat (Rattus norvegicus).

Recent data suggest that both nocturnal and diurnal mammals generate circadian rhythms using similarly phased feedback loops involving Period genes in the suprachiasmatic nuclei (SCN) of the hypothalamus. These molecular oscillations also exist in the brain outside of the SCN, but the relationship between SCN and extra-SCN oscillations is unclear. We hypothesized that a comparison of "diurnal" and "nocturnal" central nervous system Per rhythms would uncover differences in the underlying circadian mechanisms between these two chronotypes. Therefore, this study compared the 24-h oscillatory patterns of Per1 and Per2 mRNA in the SCN and putative striatum and cortex of Octodon degus (degu), a diurnal hystricognath rodent, with those of the nocturnal laboratory rat, Rattus norvegicus. The brains of adult male degus and rats were collected at 2-h intervals across 24 h in entrained light-dark and constant darkness conditions, and sections were analyzed via in situ hybridization. In the SCN, degu Per1 and Per2 hybridization signal exhibited 24-h oscillatory patterns similar in phasing to those seen in other rodents, with peaks occurring during the light period and troughs during the dark period. However, Per1 remained elevated for five fewer hours in the degu than in the rat, and Per2 remained elevated for two fewer hours in the degu. In brain areas outside of the SCN, the phase of Per2 hybridization signal rhythms in the degu were 180 degrees out of phase with those found in the rat, and Per1 hybridization signal lacked significant rhythmicity. These results suggest that, while certain basic components of the transcriptional-translational feedback loop generating circadian rhythms are similar in diurnal and nocturnal mammals, there are variations that may reflect adaptations to circadian niche.

Vasoactive intestinal peptide and the mammalian circadian system.

In mammals, the circadian oscillators that drive daily behavioral and endocrine rhythms are located in the hypothalamic suprachiasmatic nucleus (SCN). While the SCN is anatomically well-situated to receive and transmit temporal cues to the rest of the brain and periphery, there are many holes in our understanding of how this temporal regulation occurs. Unanswered questions include how cell autonomous circadian oscillations within the SCN remain synchronized to each other as well as communicate temporal information to downstream targets. In recent years, it has become clear that neuropeptides are critically involved in circadian timekeeping. One such neuropeptide, vasoactive intestinal peptide (VIP), defines a cell population within the SCN and is likely used as a signaling molecule by these neurons. Converging lines of evidence suggest that the loss of VIP or its receptor has a major influence on the ability of the SCN neurons to generate circadian oscillations as well as synchronize these cellular oscillations. VIP, acting through the VPAC(2) receptor, exerts these effects in the SCN by activating intracellular signaling pathways and, consequently, modulating synaptic transmission and intrinsic membrane currents. Anatomical evidence suggests that these VIP expressing neurons connect both directly and indirectly to endocrine and other output targets. Striking similarities exist between the role of VIP in mammals and the role of Pigment Dispersing Factor (PDF), a functionally related neuropeptide, in the Drosophila circadian system. Work in both mammals and insects suggests that further research into neuropeptide function is necessary to understand how circadian oscillators work as a coordinated system to impose a temporal structure on physiological processes within the organism.