Rapid down-regulation of mammalian period genes during behavioral resetting of the circadian clock.
(33/2081)
The pervasive role of circadian clocks in regulating physiology and behavior is widely recognized. Their adaptive value is their ability to be entrained by environmental cues such that the internal circadian phase is a reliable predictor of solar time. In mammals, both light and nonphotic behavioral cues can entrain the principal oscillator of the hypothalamic suprachiasmatic nuclei (SCN). However, although light can advance or delay the clock during circadian night, behavioral events trigger phase advances during the subjective day, when the clock is insensitive to light. The recent identification of Period (Per) genes in mammals, homologues of dperiod, which encodes a core element of the circadian clockwork in Drosophila, now provides the opportunity to explain circadian timing and entrainment at a molecular level. In mice, expression of mPer1 and mPer2 in the SCN is rhythmic and acutely up-regulated by light. Moreover, the temporal relations between mRNA and protein cycles are consistent with a clock based on a transcriptional/translational feedback loop. Here we describe circadian oscillations of Per1 and Per2 in the SCN of the Syrian hamster, showing that PER1 protein and mRNA cycles again behave in a manner consistent with a negative-feedback oscillator. Furthermore, we demonstrate that nonphotic resetting has the opposite effect to light: acutely down-regulating these genes. Their sensitivity to nonphotic resetting cues supports their proposed role as core elements of the circadian oscillator. Moreover, this study provides an explanation at the molecular level for the contrasting but convergent effects of photic and nonphotic cues on the clock. (+info)
Arousal in patients with gastro-oesophageal reflux and sleep apnoea.
(34/2081)
Nocturnal gastro-oesophageal reflux has been observed in patients with obstructive sleep apnoea (OSA). Negative intrathoracic pressure during apnoeas and arousal have been suggested as the underlying mechanisms. In order to evaluate this hypothesis, the coincidence and sequence in time of arousal, apnoea and reflux events were analysed. Fifteen patients with OSA or heavy snoring were studied by means of standard polysomnograpy with parallel recording of 24-h oesophageal pH. Reflux events during the day were present in all patients, five of whom had symptoms of reflux. In three of these and in five other patients, a total of 69 nocturnal reflux events were found. In 68 events, arousal was found with the reflux event. Only one reflux without arousal was found (sleep stage 2). Seventeen events occurred during wakefulness after sleep onset. The percentage of time with a pH of <4 during wakefulness after sleep onset was significantly higher than the percentage of time with a pH of <4 during total sleep time (p<0.05). In 37 of the 52 reflux events which occurred during sleep, either an apnoea or a hypopnoea was found prior to the event. The investigation of sequence in time did not prove a causal relation between respiratory events and reflux events. The results indicate that gastro-oesophageal reflux and obstructive sleep apnoea are two separate disorders, which both have a high prevalence in obese patients. (+info)
Destabilizing effects of mental stress on ventricular arrhythmias in patients with implantable cardioverter-defibrillators.
(35/2081)
BACKGROUND: The incidence of sudden cardiac death increases in populations who experience disasters such as earthquakes. The physiological link between psychological stress and sudden death is unknown; one mechanism may be the direct effects of sympathetic arousal on arrhythmias. To determine whether mental stress alters the induction, rate, or termination of ventricular arrhythmias, we performed noninvasive programmed stimulation (NIPS) in patients with defibrillators and ventricular tachycardia (VT), which is known to be inducible and terminated by antitachycardia pacing, at rest and during varying states of mental arousal. METHODS AND RESULTS: Eighteen patients underwent NIPS in the resting-awake state (nonsedated). Ten underwent repeat testing during mental stress (mental arithmetic and anger recall). Induced VT was faster in 5 patients (P=0.03). VT became more difficult to terminate in 5 patients during mental stress; 4 required a shock (P=0.03). There was no change in ease of induction with mental stress. There was no evidence of ischemia on ECG or continuous ejection fraction monitoring. Eight patients received a shock in the resting-awake state and did not perform mental stress. Four underwent repeat NIPS after sedation; 3 then had induced VT terminated with antitachycardia pacing. All patients with an increase in norepinephrine of >50% had alterations in VT that required shock for termination (P<0.01). CONCLUSIONS: Mental stress alters VT cycle length and termination without evidence of ischemia. This suggests that mental stress may lead to sudden death through the facilitation of lethal ventricular arrhythmias. (+info)
Does sleep fragmentation impact recuperation? A review and reanalysis.
(36/2081)
Studies have shown that next-day performance and alertness are impaired by sleep fragmentation procedures even when total sleep time (TST) is unaffected. Based on these studies it has been hypothesized that both the duration and continuity of sleep determine its recuperative value. This review of the literature suggests that when sleep fragmentation procedures increase the relative amount of stage 1 sleep, next-day performance and alertness are impaired. Other studies suggest that stage 1 sleep has little or no recuperative value. Total sleep time, however, is typically defined as the sum of time spent in sleep stages 1, 2, 3, 4, and REM. In the present paper it is shown that when stage 1 sleep is excluded from TST, a stronger relationship between TST and subsequent alertness and performance emerges--and the need to invoke 'sleep continuity' as a variable that contributes independently to recuperative sleep processes is obviated. In the same way that partial or total sleep deprivation impairs alertness and performance, it is proposed that sleep disruption also impairs alertness and performance by reducing true recuperative sleep time. (+info)
Level of arousal and the ability to maintain wakefulness.
(37/2081)
The ability to maintain wakefulness under baseline and sleep deprivation conditions was examined in a group of 14 normal young adults. Subjects participated in both standard and manipulation Maintenance of Wakefulness tests after being awake for 7, 19, and 31 h. In the manipulation Maintenance of Wakefulness tests, subjects performed varying degrees of physical activity at the onset of stage 1 to allow them to preserve wakefulness. As expected, ability to maintain wakefulness declined as time awake increased. With amount of time awake held constant, wakefulness was enhanced most after standing and doing knee bends, less after standing, less after sitting up, and least after subjects were spoken to. The improvement in alertness after doing knee bends as compared to being spoken to was of the same relative magnitude as the decrease in alertness after one night of total sleep deprivation. As expected, heart rate also increased consistently as activity increased. Each subject had a negative correlation between their EEG sleep latencies and their minimum r-r interval during the manipulation, i.e. the higher the heart rate, the longer the latency. These data were interpreted as a demonstration of the impact of discrete phasic arousal on the ability to maintain wakefulness. (+info)
Ventilatory and arousal responses of sleeping lambs to respiratory challenges: effect of prenatal maternal anemia.
(38/2081)
We have examined the effects of exposure to chronic maternal anemia, throughout the final one-third of gestation, on postnatal ventilatory and arousal responses to hypoxia, hypercapnia, and combined hypoxia-hypercapnia in sleeping lambs. While resting quietly awake, lambs from anemic ewes had higher arterial PCO(2) levels than control animals during the first 2-3 postnatal wk, but pH, arterial PO(2), and arterial O(2) saturation were not different. During active and quiet sleep lambs from anemic ewes had higher end-tidal CO(2) levels than control animals when breathing room air and at the time of spontaneous arousal or when aroused by progressive hypercapnia or by combined hypoxia-hypercapnia. Ventilation and arterial O(2) saturation during uninterrupted sleep and ventilatory responsiveness to hypoxia (inspiratory O(2) fraction, 10%), progressive hypercapnia, and combined hypoxia/hypercapnia were not significantly affected by exposure to maternal anemia. Our findings show that maternal anemia results in elevated PCO(2) levels in the offspring. This effect may be due, at least in part, to altered pulmonary function. (+info)
Investigation of nonlinear ECoG changes during spontaneous sleep state changes and cortical arousal in fetal sheep.
(39/2081)
We examined the processes of cortical activation and deactivation of the fetal brain during spontaneous sleep state transitions and during central nervous processing of vibroacoustic stimulations (VASs) using nonlinear analysis of the electrocorticogram (ECoG). Tests of nonlinearity and a random shuffling routine revealed deterministic and nonlinear portions in the fetal ECoG. As common nonlinear measures are not applicable to nonstationary time series, we developed an algorithm to estimate the predictability of the ECoG in its time course by means of a point prediction error (PPE). The ECoG was recorded before and during VAS from the maternal abdominal surface in seven chronically instrumented fetal sheep at 0.8 of gestation. The PPE during REM sleep was significantly higher than during NREM sleep. VAS in NREM sleep resulted in an abrupt increase of the PPE not reaching the level of REM sleep. The steep increase of the PPE at onset and its slow decrease after cessation of the stimulus were very similar to the dynamics of spontaneous sleep state transitions, suggesting the involvement of the same cortical activating mechanisms. In conclusion, the stage and the time course of fetal brain activation and deactivation patterns can be clearly shown by PPE techniques. The PPE is a useful complement to spectral analysis. Both techniques describe different properties of the ECoG. (+info)
Control of cricket stridulation by a command neuron: efficacy depends on the behavioral state.
(40/2081)
Crickets use different song patterns for acoustic communication. The stridulatory pattern-generating networks are housed within the thoracic ganglia but are controlled by the brain. This descending control of stridulation was identified by intracellular recordings and stainings of brain neurons. Its impact on the generation of calling song was analyzed both in resting and stridulating crickets and during cercal wind stimulation, which impaired the stridulatory movements and caused transient silencing reactions. A descending interneuron in the brain serves as a command neuron for calling-song stridulation. The neuron has a dorsal soma position, anterior dendritic processes, and an axon that descends in the contralateral connective. The neuron is present in each side of the CNS. It is not activated in resting crickets. Intracellular depolarization of the interneuron so that its spike frequency is increased to 60-80 spikes/s reliably elicits calling-song stridulation. The spike frequency is modulated slightly in the chirp cycle with the maximum activity in phase with each chirp. There is a high positive correlation between the chirp repetition rate and the interneuron's spike frequency. Only a very weak correlation, however, exists between the syllable repetition rate and the interneuron activity. The effectiveness of the command neuron depends on the activity state of the cricket. In resting crickets, experimentally evoked short bursts of action potentials elicit only incomplete calling-song chirps. In crickets that previously had stridulated during the experiment, short elicitation of interneuron activity can trigger sustained calling songs during which the interneuron exhibits a spike frequency of approximately 30 spikes/s. During sustained calling songs, the command neuron activity is necessary to maintain the stridulatory behavior. Inhibition of the interneuron stops stridulation. A transient increase in the spike frequency of the interneuron speeds up the chirp rate and thereby resets the timing of the chirp pattern generator. The interneuron also is excited by cercal wind stimulation. Cercal wind stimulation can impair the pattern of chirp and syllable generation, but these changes are not reflected in the discharge pattern of the command neuron. During wind-evoked silencing reactions, the activity of the calling-song command neuron remains unchanged, but under these conditions, its activity is no longer sufficient to maintain stridulation. Therefore stridulation can be suppressed by cercal inputs from the terminal ganglia without directly inhibiting the descending command activity. (+info)