Chronotype predicts positive affect rhythms measured by ecological momentary assessment

Evening chronotype, a correlate of delayed circadian rhythms, is associated with depression. Altered positive affect (PA) rhythms may mediate the association between evening chronotype and depression severity. Consequently, a better understanding of the relationship between chronotype and PA may aid in understanding the etiology of depression. Recent studies have found that individuals with evening chronotype show delayed and blunted PA rhythms, although these studies are relatively limited in sample size, representativeness and number of daily affect measures. Further, published studies have not included how sleep timing changes on workday and non-workdays, or social jet lag (SJL) may contribute to the chronotype-PA rhythm link. Healthy non-depressed adults (n?=?408) completed self-report affect and chronotype questionnaires. Subsequently, positive and negative affects were measured hourly while awake for at least two workdays and one non-workday by ecological momentary assessment (EMA). Sleep variables were collected via actigraphy and compared across chronotype groups. A cosinor variant of multilevel modeling was used to model individual and chronotype group rhythms and to calculate two variables: (1) amplitude of PA, or the absolute amount of daily variation from peak to trough during one period of the rhythm and (2) acrophase, or the time at which the peak amplitude of affect rhythms occurred. On workdays, individuals with evening chronotype had significantly lower PA amplitudes and later workday acrophase times than their morning type counterparts. In contrast to predictions, SJL was not found to be a mediator in the relationship between chronotype and PA rhythms. The association of chronotype and PA rhythms in healthy adults may suggest the importance of daily measurement of PA in depressed individuals and would be consistent with the hypothesis that evening chronotype may create vulnerability to depression via delayed and blunted PA rhythms.     

Rats with minimal hepatic encephalopathy show reduced cGMP-dependent protein kinase activity in hypothalamus correlating with circadian rhythms alterations

Patients with liver cirrhosis show disturbances in sleep and in its circadian rhythms which are an early sign of minimal hepatic encephalopathy (MHE). The mechanisms of these disturbances are poorly understood. Rats with porta-caval shunt (PCS), a model of MHE, show sleep disturbances reproducing those of cirrhotic patients. The aims of this work were to characterize the alterations in circadian rhythms in PCS rats and analyze the underlying mechanisms. To reach these aims, we analyzed in control and PCS rats: (a) daily rhythms of spontaneous and rewarding activity and of temperature, (b) timing of the onset of activity following turning-off the light, (c) synchronization to light after a phase advance and (d) the molecular mechanisms contributing to these alterations in circadian rhythms. PCS rats show altered circadian rhythms of spontaneous and rewarding activities (wheel running). PCS rats show more rest bouts during the active phase, more errors in the onset of motor activity and need less time to re-synchronize after a phase advance than control rats. Circadian rhythm of body temperature is also slightly altered in PCS rats. The internal period length (tau) of circadian rhythm of motor activity is longer in PCS rats. We analyzed some mechanisms by which hypothalamus modulate circadian rhythms. PCS rats show increased content of cGMP in hypothalamus while the activity of cGMP-dependent protein kinase was reduced by 41% compared to control rats. Altered cGMP-PKG pathway in hypothalamus would contribute to altered circadian rhythms and synchronization to light.     

Stability and Fragmentation of the Activity Rhythm Across the Sleep-Wake Cycle: The Importance of Age,Lifestyle, and Mental Health

The rhythms of activity across the 24-h sleep-wake cycle, determined in part by the circadian clock, change with aging. Few large-scale studies measured the activity rhythm objectively in the general population. The present population-based study in middle-aged and elderly persons evaluated how activity rhythms change with age, and additionally investigated sociodemographics, mental health, lifestyle, and sleep characteristics as determinants of rhythms of activity. Activity rhythms were measured objectively with actigraphy. Recordings of at least 96?h (138?±?14?h, mean?±?SD) were collected from 1734 people (age: 62?±?9.4?yrs) participating in the Rotterdam Study. Activity rhythms were quantified by calculating interdaily stability, i.e., the stability of the rhythm over days, and intradaily variability, i.e., the fragmentation of the rhythm relative to its 24-h amplitude. We assessed age, gender, presence of a partner, employment, cognitive functioning, depressive symptoms, body mass index (BMI), coffee use, alcohol use, and smoking as determinants. The results indicate that older age is associated with a more stable 24-h activity profile (β?=?0.07, p?=?0.02), but also with a more fragmented distribution of periods of activity and inactivity (β?=?0.20, p?<?0.001). Having more depressive symptoms was related to less stable (β?=??0.07, p?=?0.005) and more fragmented (β?=?0.10, p?<?0.001) rhythms. A high BMI and smoking were also associated with less stable rhythms (BMI: β?=??0.11, p?<?0.001; smoking: β?=??0.11, p?<?0.001) and more fragmented rhythms (BMI: β?=?0.09, p?<?0.001; smoking: β?=?0.11, p?<?0.001). We conclude that with older age the 24-h activity rhythm becomes more rigid, whereas the ability to maintain either an active or inactive state for a longer period of time is compromised. Both characteristics appear to be important for major health issues in old age.     

Effects of N-acetylcysteine and imipramine in a model of acute rhythm disruption in BALB/c mice

Circadian rhythm disturbances are among the risk factors for depression, but specific animal models are lacking. This study aimed to characterize the effects of acute rhythm disruption in mice and investigate the effects of imipramine and N-acetylcysteine (NAC) on rhythm disruption-induced changes. Mice were exposed to 12:12-hour followed by 10:10-hour light:dark cycles (LD); under the latter, mice were treated with saline, imipramine or NAC. Rhythms of rest/activity and temperature were assessed with actigraphs and iButtons, respectively. Hole-board and social preference tests were performed at the beginning of the experiment and again at the 8th 10:10 LD, when plasma corticosterone and IL-6 levels were also assessed. Actograms showed that the 10:10 LD schedule prevents the entrainment of temperature and activity rhythms for at least 13 cycles. Subsequent light regimen change activity and temperature amplitudes showed similar patterns of decline followed by recovery attempts. During the 10:10 LD schedule, activity and temperature amplitudes were significantly decreased (paired t test), an effect exacerbated by imipramine (ANOVA/SNK). The 10:10 LD schedule increased anxiety (paired t test), an effect prevented by NAC (30?mg/kg). This study identified mild but significant behavioral changes at specific time points after light regimen change. We suggest that if repeated overtime, these subtle changes may contribute to lasting behavioral disturbancess relevant to anxiety and mood disorders. Data suggest that imipramine may contribute to sustained rhythm disturbances, while NAC appears to prevent rhythm disruption-induced anxiety. Associations between sleep/circadian disturbances and the recurrence of depressive episodes underscore the relevance of potential drug-induced maintenance of disturbed rhythms.     

Age-dependent changes of the circadian system

This review summarizes the current knowledge on changes of the circadian system in advanced age, mainly for rodents. The first part is dedicated to changes of the overt rhythms. Possible causes are discussed, as are methods to treat the disturbances. In aging animals and humans, all rhythm characters change. The most prominent changes are the decrease of the amplitude and the diminished ability to synchronize with a periodic environment. The susceptibility to photic and nonphotic cues is decreased. As a consequence, both internal and external temporal order are disturbed under steady-state conditions and, even more, following changes in the periodic environment. Due to the high complexity of the circadian system, which includes oscillator(s), mechanisms of external synchronization and of internal coupling, the changes may arise for several reasons. Many of the changes seem to occur within the SCN itself. The number of functioning neurons decreases with advancing age and, probably, so does the coupling between them. As a result, the SCN is unable, or at least less able, to produce stable rhythms and to transmit timing information to target sites. Initially, only the ability to synchronize with the periodic environment is diminished, whereas the rhythms themselves continue to be well pronounced. Therefore, the possibility exists to treat age-dependent disturbances. This can be done pharmacologically or by increasing the zeitgeber strength. So, some of the rhythm disturbances can be reversed, increasing the magnitude of the light-dark (LD) zeitgeber. Another possibility is to strengthen feedback effects, for example, by increasing the daily amount of activity. By this means, the stability and synchronization of the circadian activity rhythm of old mice and men were improved. (Chronobiology International,17(3), 261-283, 2000)     

AGE-DEPENDENT CHANGES OF THE CIRCADIAN SYSTEM

This review summarizes the current knowledge on changes of the circadian system in advanced age, mainly for rodents. The first part is dedicated to changes of the overt rhythms. Possible causes are discussed, as are methods to treat the disturbances. In aging animals and humans, all rhythm characters change. The most prominent changes are the decrease of the amplitude and the diminished ability to synchronize with a periodic environment. The susceptibility to photic and nonphotic cues is decreased. As a consequence, both internal and external temporal order are disturbed under steady-state conditions and, even more, following changes in the periodic environment. Due to the high complexity of the circadian system, which includes oscillator(s), mechanisms of external synchronization and of internal coupling, the changes may arise for several reasons. Many of the changes seem to occur within the SCN itself. The number of functioning neurons decreases with advancing age and, probably, so does the coupling between them. As a result, the SCN is unable, or at least less able, to produce stable rhythms and to transmit timing information to target sites. Initially, only the ability to synchronize with the periodic environment is diminished, whereas the rhythms themselves continue to be well pronounced. Therefore, the possibility exists to treat age-dependent disturbances. This can be done pharmacologically or by increasing the zeitgeber strength. So, some of the rhythm disturbances can be reversed, increasing the magnitude of the light-dark (LD) zeitgeber. Another possibility is to strengthen feedback effects, for example, by increasing the daily amount of activity. By this means, the stability and synchronization of the circadian activity rhythm of old mice and men were improved. (Chronobiology International,17(3), 261–283, 2000)     

Circadian Rhythm in Gamma Glutamyltranspeptidase and Leucine Aminopeptidase Urinary Activity in Rats

Urinary gamma glutamyltranspeptidase (GGT) and leucine aminopeptidase (LAP), renal tubular brush border enzymes, have been shown to be sensitive indicators of renal tubular functions. This study documents circadian rhythms in the urinary activity of GGT and LAP, statistically validated and quantified by the cosinor method, in 15 male Wistar rats standardized to a LD 12:12 illumination schedule (light from 0800 hr to 2000 hr) and fed ad libitum. The acrophase of the circadian rhythms in urinary GGT and LAP activity occurred at the end of the rest span of the animals: between 1730 and 1915 for GGT (depending on the mode of expression of the activity) and between 1700 and 1910 for LAP. Of striking resemblance in their timing, both these rhythms were also of large amplitude (about 50% of the mesor for urinary GGT activity and about 45% for LAP one). The circadian acrophases of urinary GGT and LAP activity led in timing the circadian rhythms in urine volume and creatinine excretion by about 13hr. Such findings consistent with the circadian variations found by other investigators in GGT in kidney homogenates or in LAP in human urine thus reflect a periodicity in renal tubular function. The reasons for these circadian variations, still unknown at this time, are discussed. The influence recently demonstrated of the hormonal context on protein and enzyme synthesis at the tubule, and its phase relations to urinary enzyme excretion emphasize how much the circadian rhythm in urinary GGT and LAP activity is well included in the murine time structure. Therefore it should be of interest to consider the circadian rhythm in urinary GGT and LAP release as a marker rhythm of predictive value as to the side effects of nephrotoxic drugs.     

Chronic Administration of Imipramine and Lithium Changes the Phase-Angle Relationship Between the Activity and Core Body Temperature Circadian Rhythms in Rats

Evidence suggests that there is an association between the pathophysiology of depression and a disturbance of circadian rhythms. Accordingly, attention has focused on the possible effects of antidepressants on circadian rhythms. In the present study, we examined the effects of chronic administration of two clinically effective antidepressant agents, imipramine and lithium, on several circadian rhythms in the rat. Activity, core body temperature, and drinking rhythms were assessed in constant darkness (DD) and light-dark (LD) conditions. In DD, lithium significantly lengthened the circadian period of the activity, temperature, and drinking rhythms, while imipramine had no effect. In LD, both drugs significantly delayed the phase of the activity rhythm, but did not change that of the other two rhythms. As a result, the phase-angle differences between the activity and temperature rhythms significantly increased. Neither lithium nor imipramine produced any effect on the resynchronization of these rhythms after an 8-h delay in the LD cycle. These results indicate that although both drugs produced different effects on the circadian period of individual rhythms, both caused a relative phase advance of the temperature rhythm as compared to the activity rhythm, and this effect may be related to the similarity in their antidepressant effects. (Chronobiology International, 13(4), 251-259, 1996)     

Circadian Rhythm in Gamma Glutamyltranspeptidase and Leucine Aminopeptidase Urinary Activity in Rats

Urinary gamma glutamyltranspeptidase (GGT) and leucine aminopeptidase (LAP), renal tubular brush border enzymes, have been shown to be sensitive indicators of renal tubular functions. This study documents circadian rhythms in the urinary activity of GGT and LAP, statistically validated and quantified by the cosinor method, in 15 male Wistar rats standardized to a LD 12:12 illumination schedule (light from 0800 hr to 2000 hr) and fed ad libitum. The acrophase of the circadian rhythms in urinary GGT and LAP activity occurred at the end of the rest span of the animals: between 1730 and 1915 for GGT (depending on the mode of expression of the activity) and between 1700 and 1910 for LAP. Of striking resemblance in their timing, both these rhythms were also of large amplitude (about 50% of the mesor for urinary GGT activity and about 45% for LAP one). The circadian acrophases of urinary GGT and LAP activity led in timing the circadian rhythms in urine volume and creatinine excretion by about 13hr. Such findings consistent with the circadian variations found by other investigators in GGT in kidney homogenates or in LAP in human urine thus reflect a periodicity in renal tubular function. The reasons for these circadian variations, still unknown at this time, are discussed. The influence recently demonstrated of the hormonal context on protein and enzyme synthesis at the tubule, and its phase relations to urinary enzyme excretion emphasize how much the circadian rhythm in urinary GGT and LAP activity is well included in the murine time structure. Therefore it should be of interest to consider the circadian rhythm in urinary GGT and LAP release as a marker rhythm of predictive value as to the side effects of nephrotoxic drugs.     

The Utility of the Swine Model to Assess Biological Rhythms and Their Characteristics during Different Stages of Residence in a Simulated Intensive Care Unit: A Pilot Study

The purpose of this pilot study was to explore the utility of the mammalian swine model under simulated intensive care unit (sICU) conditions and mechanical ventilation (MV) for assessment of the trajectory of circadian rhythms of sedation requirement, core body temperature (CBT), pulmonary mechanics (PM) and gas exchange (GE). Data were collected prospectively with an observational time-series design to describe and compare circadian rhythms of selected study variables in four swine mechanically ventilated for up to seven consecutive days. We derived the circadian (total variance explained by rhythms of τ between 20 and 28?h)/ultradian (total variance explained by rhythms of τ between 1 and <20?h) bandpower ratio to assess the robustness of circadian rhythms, and compare findings between the early (first 3 days) and late (subsequent days) sICU stay. All pigs exhibited statistically significant circadian rhythms (τ between 20 and 28?h) in CBT, respiratory rate and peripheral oxygen saturation, but circadian rhythms were detected less frequently for sedation requirement, spontaneous minute volume, arterial oxygen tension, arterial carbon dioxide tension and arterial pH. Sedation did not appear to mask the circadian rhythms of CBT, PM and GE. Individual subject observations were more informative than group data, and provided preliminary evidence that (a) circadian rhythms of multiple variables are lost or desynchronized in mechanically ventilated subjects, (b) robustness of circadian rhythm varies with subject morbidity and (c) healthier pigs develop more robust circadian rhythm profiles over time in the sICU. Comparison of biological rhythm profiles among sICU subjects with similar severity of illness is needed to determine if the results of this pilot study are reproducible. Identification of consistent patterns may provide insight into subject morbidity and timing of such therapeutic interventions as weaning from MV.     

Circadian physiology is a toxicity target of the anticancer drug gemcitabine in mice

The circadian timing system determines the optimal timing and waveform of drug tolerability, yet treatment itself can alter this system. Gemcitabine is an antimetabolite agent that is active against lung and pancreatic cancers. Tolerability for this drug is best following dosing at ZT 11 in mice. The authors investigated the effects of gemcitabine on the circadian rhythms in body temperature and rest activity as physiological markers of the circadian timing system. Healthy unrestrained B6D2F(1) mice implanted with radiotelemetry transmitters were kept in LD 12:12 prior to receiving a single intravenous dose of gemcitabine (200, 400, or 600 mg/kg) at ZT 11 or 23. Gemcitabine (400 mg/kg) transiently suppressed the body temperature rhythm in 50% of the mice dosed at ZT 23, as compared to none of the mice treated at ZT 11 within the 2 days following drug dosing (Fisher 's exact test p = 0.04). The rest-activity circadian rhythm was suppressed in 40% (ZT 11) and 50% (ZT 23) of the mice, respectively. In the mice with persistent circadian rhythms, gemcitabine delivery at ZT 23 resulted in more prominent decreases and slower recovery of circadian mesor and amplitude of both rhythms as compared to mice treated at ZT 11. Gemcitabine also induced a transient internal desynchronization between temperature and activity rhythms following dosing at ZT 23 but not at ZT 11. The delivery of a single therapeutic dose of gemcitabine near its time of least toxicity produced least alterations in circadian physiological outputs, a finding that suggests that the extent of circadian disruption contributes to toxicokinetic processes.     

Social rhythm regularity moderates the relationship between sleep disruption and depressive symptoms in veterans with post-traumatic stress disorder and major depressive disorder

ABSTRACT

Approximately 50% to 80% of individuals with posttraumatic stress disorder (PTSD) also meet criteria for major depressive disorder (MDD). Sleep disturbance is a major concern in both PTSD and MDD, and is associated with poor treatment response, poor functional outcome and increased suicide risk. Social rhythm regularity, or the consistency of daily habitual behaviors, is theoretically linked to circadian rhythms and may be disturbed in both PTSD and MDD. The present study examined the relationship between social rhythm regularity, sleep disruption and MDD and PTSD symptoms in a sample of veterans with comorbid PTSD and MDD. Baseline data were obtained from 56 male veterans who met DSM-IV criteria for PTSD and MDD. Veterans completed the Social Rhythm Metric (SRM), a self-report questionnaire that assesses the regularity of routines by determining how regularly individuals completed 17 different types of activities. In a linear regression model, increased minutes awake after sleep onset (WASO) was a significant predictor of increased depression scores on the Hamilton Rating Scale for Depression (p < .05). SRM scores did not significantly predict depressive symptoms, however the interaction of WASO and SRM significantly predicted depressive symptoms (p = <.05), with significant relationships found at SRM scores less than 3.62. Neither minutes awake after sleep onset, SRM scores, nor their interaction was associated with PTSD symptom severity. Social and possibly circadian rhythm regularity may represent a risk or resilience factor for individuals with comorbid PTSD and MDD. Findings highlight the importance of exploring the interactions of sleep and social/circadian rhythms in depression in order to inform continued treatment development.     

Non-stationary time series and the robustness of circadian rhythms

Circadian rhythms are regular oscillations in the value of behavioral and physiological variables of organisms that recur on a daily basis. The purpose of this study was to evaluate the extent of non-stationarity of circadian rhythms over several days, to determine how damaging is the violation of the assumption of stationarity in the analysis of circadian rhythms, and to formalize the concept of "rhythm robustness" as an index of oscillatory ("weak") stationarity. Simulated (computer-generated) and experimental data sets (rhythms of body temperature and running-wheel activity in several rodent species) were analysed. Tests of stationarity based on the variance of the daily means and the variance of the daily variances revealed that most experimental data sets are not stationary. Analysis of linear trends indicated that significant trends are rare in experimental data sets. Although the non-stationarity of the experimental data sets reduced the spectral energy of the Enright periodogram used to assess rhythmicity, detection of circadian rhythmicity was not prevented in any of the rhythmic data sets. The results of the various analyses allow the inference that, after high-frequency noise is filtered out, the value of the periodogram's Q(P) statistic reflects the extent of stationarity of the time series. Thus, the "robustness" of a circadian rhythm (i.e. the magnitude of the empirical Q(P) value as compared to the Q(P) value associated with a perfectly rhythmic time series) can serve as an index of the stationarity of the rhythm.     

Sleep,daily activity rhythms and postpartum mood: A longitudinal study across the perinatal period

Women with a diagnosis of bipolar and major depressive disorders are at higher risk to develop postpartum depression. The primary objective of this longitudinal study was to determine whether daily activity rhythms and sleep parameters differ between women with and without a history of a mood disorder across the perinatal period. A secondary objective was to determine whether changes in these parameters were associated with postpartum mood. In total, 33 women were included in this study, 15 of which had a history of a mood disorder (high-risk group) and 18 who did not (low-risk group). Sleep and daily rhythms were assessed subjectively and objectively during the third trimester (≥26 weeks gestation) and again at 6–12 weeks postpartum. Mood was also assessed at both time points. Women in the high-risk group showed greater subjective daily rhythms and sleep disturbances across the perinatal period. Objective sleep efficiency was worse in the high-risk group in the postpartum period. Changes in both subjective daily rhythms and objective sleep efficiency were predictive of changes in depressive symptoms across the perinatal period. These findings encourage the development of preventative therapeutics to ensure circadian rhythm and sleep stability throughout the perinatal period.     

Differential effects of pinealectomy on circadian rhythms of feeding and perch hopping in the European starling

To study the effects of pinealectomy on the circadian rhythms of locomotor activity and feeding. European starlings (Sturnus vulgaris) were held in constant light (0.2 lux and 200 lux) and under constant temperature conditions. Locomotor activity was measured by means of perches with microswitches mounted underneath, and feeding with an infrared photocell system at the feeder. Pinealectomy consistently led to disturbances in perch-hopping rhythms and often to a complete loss of rhythmicity as revealed by periodogram analysis. In some birds, perch-hopping rhythms recovered following a period of initial arrhythmicity. When a perch-hopping rhythm was present, its period was usually shorter than it had been before pinealectomy. In contrast to its effects on perch hopping, pinealectomy had no effect on the persistence of feeding rhythmicity, although its period, like that of the hopping rhythm, decreased after this operation. These results support the hypothesis derived from previous studies that the circadian organization of feeding is different from that of perch hopping. Different circadian pacemakers may be involved, but other models may possibly explain the data just as well.     

On analyzing circadian rhythms data using nonlinear mixed models with harmonic terms

Wang, Ke, and Brown (2003, Biometrics59, 804-812) developed a smoothing-based approach for modeling circadian rhythms with random effects. Their approach is flexible in that fixed and random covariates can affect both the amplitude and phase shift of a nonparametrically smoothed periodic function. In motivating their approach, Wang et al. stated that a simple sinusoidal function is too restrictive. In addition, they stated that "although adding harmonics can improve the fit, it is difficult to decide how many harmonics to include in the model, and the results are difficult to interpret." We disagree with the notion that harmonic models cannot be a useful tool in modeling longitudinal circadian rhythm data. In this note, we show how nonlinear mixed models with harmonic terms allow for a simple and flexible alternative to Wang et al.'s approach. We show how to choose the number of harmonics using penalized likelihood to flexibly model circadian rhythms and to estimate the effect of covariates on the rhythms. We fit harmonic models to the cortisol circadian rhythm data presented by Wang et al. to illustrate our approach. Furthermore, we evaluate the properties of our procedure with a small simulation study. The proposed parametric approach provides an alternative to Wang et al.'s semiparametric approach and has the added advantage of being easy to implement in most statistical software packages.     

Multi-scale motility amplitude associated with suicidal thoughts in major depression

Major depression occurs at high prevalence in the general population, often starts in juvenile years, recurs over a lifetime, and is strongly associated with disability and suicide. Searches for biological markers in depression may have been hindered by assuming that depression is a unitary and relatively homogeneous disorder, mainly of mood, rather than addressing particular, clinically crucial features or diagnostic subtypes. Many studies have implicated quantitative alterations of motility rhythms in depressed human subjects. Since a candidate feature of great public-health significance is the unusually high risk of suicidal behavior in depressive disorders, we studied correlations between a measure (vulnerability index [VI]) derived from multi-scale characteristics of daily-motility rhythms in depressed subjects (n?=?36) monitored with noninvasive, wrist-worn, electronic actigraphs and their self-assessed level of suicidal thinking operationalized as a wish to die. Patient-subjects had a stable clinical diagnosis of bipolar-I, bipolar-II, or unipolar major depression (n?=?12 of each type). VI was associated inversely with suicidal thinking (r?=?-0.61 with all subjects and r?=?-0.73 with bipolar disorder subjects; both p<0.0001) and distinguished patients with bipolar versus unipolar major depression with a sensitivity of 91.7% and a specificity of 79.2%. VI may be a useful biomarker of characteristic features of major depression, contribute to differentiating bipolar and unipolar depression, and help to detect risk of suicide. An objective biomarker of suicide-risk could be advantageous when patients are unwilling or unable to share suicidal thinking with clinicians.     

Hypertension and disrupted blood pressure circadian rhythm in type 2 diabetic db/db mice

Human Type 2 diabetes is associated with increased incidence of hypertension and disrupted blood pressure (BP) circadian rhythm. Db/db mice have been used extensively as a model of Type 2 diabetes, but their BP is not well characterized. In this study, we used radiotelemetry to define BP and the circadian rhythm in db/db mice. We found that the systolic, diastolic, and mean arterial pressures were each significantly increased by 11, 8, and 9 mmHg in db/db mice compared with controls. In contrast, no difference was observed in pulse pressure or heart rate. Interestingly, both the length of time db/db mice were active (locomotor) and the intensity of locomotor activity were significantly decreased in db/db mice. In contrast to controls, the 12-h light period average BP in db/db mice did not dip significantly from the 12-h dark period. A partial Fourier analysis of the continuous 72-h BP data revealed that the power and the amplitude of the 24-h period length rhythm were significantly decreased in db/db mice compared with the controls. The acrophase was centered at 0141 in control mice, but became scattered from 1805 to 0236 in db/db mice. In addition to BP, the circadian rhythms of heart rate and locomotor activity were also disrupted in db/db mice. The mean arterial pressure during the light period correlates with plasma glucose, insulin, and body weight. Moreover, the oscillations of the clock genes DBP and Bmal1 but not Per1 were significantly dampened in db/db mouse aorta compared with controls. In summary, our data show that db/db mice are hypertensive with a disrupted BP, heart rate, and locomotor circadian rhythm. Such changes are associated with dampened oscillations of clock genes DBP and Bmal1 in vasculature.     

Circadian locomotory rhythm and the influence of moulting in Australian field cricket nymphs

ABSTRACT. Evidence is presented for a circadian control of locomotory activity in the larval stadia of the cricket, Teleogryllus commodus Walker. Under light—dark cycles (LD), maximal activity occurs around the L/D transition and/or in the hours preceding it. Free-running rhythm patterns longer than 24 h are observed in constant light. Re-entrainment to phase advances in the LD cycle is also accompanied by several transient cycles. However, free-running rhythms under constant darkness or transients when exposed to LD cycle delays were not found. LD cycles during the eighth stadium set the phase of a free-running rhythm in the adult, even if the nymph does not show a rhythm. Nymphal activity is often erratic and is disrupted periodically by the moulting cycle, but moulting does not interrupt the operation of the circadian system. The daily timing of the moult itself is not under circadian control.