Phase-shifts of apparent circadian rhythms due to west and east transmeridian flights or to corresponding night-shift sleep displacements

Phase movements of apparent circadian rhythms during 2 wk of forward or backward displacement of the sleep-wake cycle were investigated in four experimental series in a subject. The 7-hr delay or advance of sleep due to a westward or an eastward transmeridian flight was duplicated by corresponding sleep displacements during experimental night shifts. Sudden phase advances (or delays) by several hours were observed in the rhythms of continuously recorded rectal temperature and urinary excretion rates (4-hr collection intervals) of adrenaline, noradrenaline and aldosterone the first day after sleep-wake displacement. The desired 7-hr phase-shifts were reached more quickly and completely when the phase was delayed than when it was advanced. In addition, the best-fitting period of these rhythms became shorter than 24 hr when the phase was delayed, and longer than 24 hr when it was advanced. The apparent rhythms of urine flow and electrolyte excretions (potassium, sodium, zinc) were much weaker and their phase movements more irregular than those of hormonal excretion. It is concluded that the sudden phase-shifts resulted from the immediate adaptation of the exogenous components of the rhythms to the demands of the displaced sleep-wake patterns (masking effects) and that the true phase-shifts of the endogenous components followed more slowly and gradually.     

Transition Between Advance and Delay Responses to Eastbound Transmeridian Flights

In response to eastbound transmeridian flights, which result in zeitgeber phase advance shifts, adaptation of the circadian system to the new time zone by phase delays and advances are observed. The delay response to an advance zeitgeber shift has been called an antidromic response. For the shift at which the transition from an advance to an antidromic response occurs, the term critical shift is introduced.

For the study of critical shifts, a flight experiment across nine time zones and numerical simulations of a van der Pol equation have been evaluated. The interest is focussed on the determination of a range for critical abrupt shifts. An abrupt shift means that the ensemble of zeitgebers including geophysical zeitgebers and the rest-activity cycle is shifted immediately in the new time zone. The range of critical advance shifts has been estimated to reach from + 7 to + 10 hr. In the literature, results were reported which would imply a much wider range. The discussion of these observations shows that the actual shifts were presumably not abrupt in the quoted experiments.

The consequences of critical shifts for jet lag symptoms are investigated. If reduced circadian amplitudes and long times taken for the resynchronization contribute to the feeling of jet lag, the symptoms will be worst for shifts close to the critical one, as numerical simulations revealed. Manipulations of such shifts with the aim to alleviate jet lag are discussed.     

Characteristics of Food-Entrained Orcadian Rhythms in Rats During Long-Term Exposure to Constant Light

Rats possess a system of circadian oscillators that permit entrainment of circadian activity rhythms independently to 24 hr cycles of light-dark and food access. The nature of interactions between food- and light-entrainable oscillators was examined by observing the generation and persistence of food-entrained circadian rhythms in rats whose light-entrainable rhythms were eliminated by long-term exposure to constant light. Most of these rats showed a delayed generation of food-entrained rhythms and only one of eight animals showed persistence of food associated rhythms during a 4-day food deprivation test. Rats whose light-entrainable rhythms are eliminated by suprachiasmatic nuclei ablation show, in contrast, normal generation and persistence of food-entrained rhythms. The results suggested a disruptive influence of constant light on non-photic entrainment, possibly due to coupling forces between damped light-entrainable oscillators and the food-entrainable oscillators.     

Characteristics of Food-Entrained Orcadian Rhythms in Rats During Long-Term Exposure to Constant Light

Rats possess a system of circadian oscillators that permit entrainment of circadian activity rhythms independently to 24 hr cycles of light-dark and food access. The nature of interactions between food- and light-entrainable oscillators was examined by observing the generation and persistence of food-entrained circadian rhythms in rats whose light-entrainable rhythms were eliminated by long-term exposure to constant light. Most of these rats showed a delayed generation of food-entrained rhythms and only one of eight animals showed persistence of food associated rhythms during a 4-day food deprivation test. Rats whose light-entrainable rhythms are eliminated by suprachiasmatic nuclei ablation show, in contrast, normal generation and persistence of food-entrained rhythms. The results suggested a disruptive influence of constant light on non-photic entrainment, possibly due to coupling forces between damped light-entrainable oscillators and the food-entrainable oscillators.     

Regression Models for the Estimation of Orcadian Rhythms in the Presence of Effects Due to Masking

The estimation of human circadian rhythms from experimental data is complicated by the presence of “masking” effects associated with the sleep-wake cycle. The observed rhythm may include a component due to masking, as well as the endogenous component linked to a circadian pacemaker. In situations where the relationship between the sleep-wake cycle and the circadian rhythm is not constant, it may be possible to obtain individual estimates of these two components, but methods commonly used for the estimation of circadian rhythms, such as the cosinor analysis, spectral analysis, average waveforms and complex demodulation, have not generally been adapted to identify the modulations that arise from masking. The estimates relate to the observed rhythms, and the amplitudes and acrophases do not necessarily refer to the endogenous rhythm.

In this paper methods are discussed for the separation of circadian and masking effects using regression models that incorporate a sinusoidal circadian variation together with functions of time since sleep and time during sleep. The basic model can be extended to include a time-varying circadian rhythm and estimates are available for the amplitude and phase at a given time, together with their joint confidence intervals and tests for changes in amplitude and acrophase between any two selected times. Modifications of these procedures are discussed to allow for non-sinusoidal circadian rhythms, non-additivity of the circadian and time-since-sleep effects and the breakdown of the usual assumptions concerning the residual errors.

This approach enables systematic masking effects associated with the sleep-wake cycle to be separated from the circadian rhythm, and it has applications to the analysis of data from experiments where the sleep-wake cycle is not synchronized with the circadian rhythm, for example after time-zone transitions or during irregular schedules of work and rest.     

Changes in Endocrine Orcadian Rhythms as Markers of Physiological and Pathological Brain Aging

We studied the circadian rhythm of plasma melatonin, growth hormone (GH), prolactin (PRL), adrenocorticotropic hormone (ACTH), and Cortisol in 52 mentally healthy old subjects, 35 old demented patients, and 22 clinically healthy young controls. When compared to young controls, the circadian profile of plasma melatonin of old subjects, both demented or not, was clearly flattened, particularly during the night. The selective impairment of nocturnal melatonin secretion was significantly related to both the age and the severity of mental impairment (Mini Mental State Examination [MMSE] score). The PRL and GH circadian profiles were similar in the three groups during the day, but a significant lowering of the values recorded during the night occurred with aging. The impairment of the nocturnal secretion was related to the subjects' age and, for the GH secretory pattern only, also to the MMSE score. The ACTH circadian profile was similar in the three groups studied, even when old subjects exhibited higher ACTH levels throughout the 24h cycle, compared to young controls. Significantly higher Cortisol values at evening- and nighttime occurred in elderly subjects and particularly in the demented group. Both the mean levels and the nadir values of plasma Cortisol were positively related to age and negatively to MMSE score. In order to verify the sensitivity of the hypothalamo-pituitary-adrenal (HPA) axis to the steroid feedback, the circadian profile of plasma Cortisol was evaluated also after dexamethasone (DXM) administration (1 mg at 23:00h); the sensitivity of the HPA axis was significantly impaired in old subjects and particularly in the demented ones. These findings suggest that the neuroendocrine alterations already present in physiological aging, due to both anatomical damages and unbalanced central neurotransmitters, are enhanced in senile dementia. (Chronobiology International, 14(4), 385–396, 1997)     

Recording and Analysis of Circadian Rhythms in Running-wheel Activity in Rodents

When rodents have free access to a running wheel in their home cage, voluntary use of this wheel will depend on the time of day^1-5. Nocturnal rodents, including rats, hamsters, and mice, are active during the night and relatively inactive during the day. Many other behavioral and physiological measures also exhibit daily rhythms, but in rodents, running-wheel activity serves as a particularly reliable and convenient measure of the output of the master circadian clock, the suprachiasmatic nucleus (SCN) of the hypothalamus. In general, through a process called entrainment, the daily pattern of running-wheel activity will naturally align with the environmental light-dark cycle (LD cycle; e.g. 12 hr-light:12 hr-dark). However circadian rhythms are endogenously generated patterns in behavior that exhibit a ~24 hr period, and persist in constant darkness. Thus, in the absence of an LD cycle, the recording and analysis of running-wheel activity can be used to determine the subjective time-of-day. Because these rhythms are directed by the circadian clock the subjective time-of-day is referred to as the circadian time (CT). In contrast, when an LD cycle is present, the time-of-day that is determined by the environmental LD cycle is called the zeitgeber time (ZT).Although circadian rhythms in running-wheel activity are typically linked to the SCN clock^6-8, circadian oscillators in many other regions of the brain and body^9-14 could also be involved in the regulation of daily activity rhythms. For instance, daily rhythms in food-anticipatory activity do not require the SCN^15,16 and instead, are correlated with changes in the activity of extra-SCN oscillators^17-20. Thus, running-wheel activity recordings can provide important behavioral information not only about the output of the master SCN clock, but also on the activity of extra-SCN oscillators. Below we describe the equipment and methods used to record, analyze and display circadian locomotor activity rhythms in laboratory rodents.