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Biomedical subjects

F W Turek

Publications and source records attributed to F W Turek.

At least 163 records · Page 9Linked to original sources

Adaptation of circadian rhythmicity to shift in light-dark cycle accelerated by a benzodiazepine.

The light-dark cycle is the major synchronizing agent for circadian rhythms in animals. After an abrupt shift in the light-dark cycle, it usually takes many days for circadian rhythms to resynchronize. A single injection of the short-acting benzodiazepine, triazolam, to hamsters subjected to an 8-h advance of the light-dark cycle resulted in an approximately 50% reduction in the time taken for the circadian locomotor activity rhythm to be resynchronized to the new lighting schedule. These results suggest that it may be possible to use drugs to facilitate the resynchronization of human circadian rhythms following an abrupt change in environmental time.

Activity Cycles↗

Entrainment of the circadian activity rhythm to the light-dark cycle can be altered by a short-acting benzodiazepine, triazolam.

The circadian rhythm of locomotor activity in hamsters maintained in either constant darkness or constant light can be phase-shifted by a single injection of the short-acting benzodiazepine, triazolam. These results suggest that treatment with triazolam may also alter the entrainment pattern of circadian rhythms in animals that are synchronized to a light-dark (LD) cycle. To test this hypothesis, hamsters maintained on an LD 6:18 light cycle received daily injections of triazolam (or vehicle) for 10-12 days, and any subsequent effects on the phase relationship between the onset of activity and the LD cycle were determined. Daily injections of triazolam (but not vehicle) induced pronounced advances or delays in the phase relationship between the entrained activity rhythm and the LD cycle; the direction of the shift was dependent on the time of the injection. Taken together with data from previous studies, these results suggest that triazolam, and perhaps other short-acting benzodiazepines, can be used to manipulate the mammalian circadian clock under a variety of experimental conditions.

Animals↗

Horizontal knife cuts either ventral or dorsal to the hypothalamic paraventricular nucleus block testicular regression in golden hamsters maintained in short days.

The possible involvement of efferent pathways from the suprachiasmatic nucleus (SCN) in the photoperiodic regulation of reproduction was studied by measuring the testis size of hamsters bearing a horizontal knife cut either ventral or dorsal to the hypothalamic paraventricular nucleus (PVN) that were transferred from photostimulatory long days (light:dark (L:D) 14:10 h) to non-stimulatory short days (L:D 6:18 h). Knife cuts placed either ventral or dorsal to the PVN blocked testicular regression induced by exposure to short days. These results indicate that efferent fibers running dorsally from the SCN to the PVN are involved in relaying photoperiodic information from the SCN to the PVN. Furthermore, recently-defined efferents that leave the PVN dorsally and terminate in the spinal cord appear to be responsible for relaying seasonal information about day-length to the pineal-reproductive axis of hamsters.

Animals↗

Circadian and photoperiodic effects of brief light pulses in male Djungarian hamsters.

The effects of brief light pulses (1-60 min in duration) on the circadian rhythm of locomotor activity and/or the neuroendocrine-gonadal axis was investigated in male Djungarian hamsters. Exposure of hamsters free-running in constant darkness to a single 1-h pulse of light induced phase-dependent phase shifts in the rhythm of locomotor activity. The general shape of the "phase-response curve" was similar to that observed in other animals; phase-delays and phase-advances were induced by light pulses delivered in the early and late subjective night, respectively, while light pulses during the subjective day induced little or no phase-shift in the activity rhythm. Animals exposed for 7 days to 1-min of light during the night in animals otherwise exposed to 6L:18D resulted in increased levels of serum FSH and testicular weight. Daily exposure to two 1-h or two 10-min pulses of light (but not two 1-min pulses) for 10 days resulted in stable entrainment of the activity rhythm as well as testicular weight gains and serum FSH increases. When two 10-min pulses of light were presented 8 and 16 h apart, some animals showed a short-day entrainment pattern (i.e., locomotor activity confined to the long period of darkness) while other animals showed a long-day entrainment pattern (i.e., locomotor activity confined to the short period of darkness). Importantly, the stimulatory effects of light on neuroendocrine-gonadal activity were clearly dependent on the phase-relationship between the light pulses and the circadian rhythm of locomotor activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Circadian principles and design of rotating shift work schedules.

Circadian rhythms may be disrupted when shift workers rotate from one work schedule to another. It has been suggested that in order to minimize the time needed to readjust circadian rhythms to a new work schedule the work time of shift workers should be rotated in a delaying rather than an advancing direction. However, delaying or advancing the work time does not imply that the sleep-wake cycle is also shifted in a similar manner. Indeed, after a complete rotation between the day, evening, and night shifts the sleep time will be advanced once, delayed once, and not shifted once, regardless of whether the workers are on a delaying or an advancing work rotation schedule. Thus circadian rhythms are likely to be perturbed in a similar manner whether the work schedule is rotated in a delaying or an advancing direction.

Circadian Rhythm↗

Multiple circadian oscillators regulate the timing of behavioral and endocrine rhythms in female golden hamsters.

A single daily "surge" in pituitary luteinizing hormone release was observed in ovariectomized-estrogen-treated hamsters expressing an intact circadian rhythm of locomotor activity. In contrast, two luteinizing hormone surges occurred within a single 24-hour period in hamsters whose activity rhythm had dissociated or "split" into two distinct components. These observations indicate that both behavioral and endocrine circadian rhythms are regulated by the same multioscillator system, which seems to be composed of at least two distinct circadian oscillators.

Animals↗

Neurochemical basis for the photic control of circadian rhythms and seasonal reproductive cycles: role for acetylcholine.

A pharmacological approach was used to examine the role of acetylcholine in the photic control of circadian rhythms and seasonal reproductive cycles. The experimental protocol was designed to determine whether the administration of carbachol, a cholinergic agonist, could mimic the effects of brief light pulses on gonadal function and/or the circadian rhythm of wheel-running activity in golden hamsters. Intraventricular injections of carbachol, administered singularly at discrete phase points throughout the circadian cycle, induced phase-dependent shifts in the free-running rhythm of activity similar to those caused by a brief light exposure. Injections of carbachol once every 23.33 hr for 9 weeks entrained the activity rhythm and stimulated the neuroendocrine-gonadal axis in a manner similar to that observed after the presentation of 1-hr light pulses at this frequency. In contrast, the administration of carbachol once every 24 hr did not consistently provide an entraining signal for the activity rhythm and did not stimulate reproductive function. Importantly, the effects of carbachol on the seasonal reproductive response were correlated with the timing of the injections relative to the activity rhythm. These findings suggest that acetylcholine may play an important role in the mechanism by which light regulates circadian rhythms and seasonal reproductive cycles.

Acetylcholine↗

Photoperiodic control of testicular size in the golden hamster: lack of a role for the deep pineal gland.

Removal of the superficial pineal gland prevents testicular regression from occurring in golden hamsters exposed to a short-day photoperiod, but to date no studies have examined the role of the deep pineal gland in the photoperiodic control of gonadal function. We investigated the role of the deep pineal gland in this process by monitoring testicular size in hamsters with an electrolytic lesion of the deep pineal gland. Sexually mature hamsters that had been sham-lesioned or that had received a lesion aimed at the deep pineal gland were transferred from 14L:10D to 6L:18D or were maintained in 14L:10D for 73 d. Testicular widths were determined at 2-3-wk intervals and after 73 d the testes were removed and weighed. The mean testis widths of the seven animals with histologically confirmed deep pineal lesions and exposed to 14L:10D remained large, similar to those of the sham-operated control animals exposed to the same photoperiod. The testes regressed in the five animals with confirmed deep pineal lesions and exposed to 6L:18D in a similar manner to those of the sham-operated control animals exposed to the same photoperiod. No significant difference (P greater than .05) was found between the testicular weights of lesioned and unlesioned animals exposed to either photoperiod. The lack of a significant effect of a deep pineal lesion on testicular size demonstrates that this portion of the pineal complex is not required for normal regulation of testicular function by photoperiod. These results also suggest that nerve fibres projecting from the brain to the superficial pineal gland via the deep pineal gland are not involved in photoperiodic regulation of testicular function.

Animals↗

Circadian neural rhythms in mammals.

A number of different experimental findings indicate that endogenous circadian neural rhythms are generated within the SCN region of mammals. Rhythmic neural signals from the SCN directly, or indirectly, appear to regulate many, if not all, biochemical, physiological, and behavioral circadian rhythms. The circadian system in mammals is referred to as being "multioscillatory" in nature, although this term is often used to mean different things. The SCN itself may contain many circadian neural oscillators and the coordinated output of these multioscillators may regulate circadian rhythms. The term multioscillatory is also used to indicate the presence of anatomically distinct oscillators. However, the location and properties of circadian pacemakers that may lie outside of the SCN region remain unknown. Indeed, there is no conclusive evidence that circadian rhythms can be generated over a prolonged period of time in the absence of the SCN in mammals maintained under constant environmental conditions. Whereas the SCN appears capable of generating circadian neural signals indefinitely in the absence of any 24-hr fluctuations in the external environment, other components of the circadian system may function as damped oscillators (i.e. persist for only a few cycles in the absence of a periodic input) and/or only emit diurnal rhythms in the presence of rhythmic input from either the external (e.g. light-dark cycle) and/or internal (e.g. SCN) environment. On a conceptual as well as a physiological level, our understanding of the organization of the mammalian circadian system remains limited at the present time. Unfortunately, the limitations on our understanding of the circadian system are not always fully appreciated, and quite often a hypothesis based on limited experimental data is treated as fact. The study of the circadian system is still in the early stages of development, and further progress in elucidating the physiological mechanisms underlying the generation and expression of circadian rhythms may require new ways of looking at old problems as well as new experimental approaches. One final comment should be made concerning the importance of an increased understanding of circadian rhythms for human health. Because the study of the physiology of the circadian system is still in its early stages of development, little is known about the importance of the normal functioning of the circadian system for the health and well-being of the organism. Recent studies in humans suggest that disorders within the circadian system itself may be involved in the etiology of at least some forms of mental illness.

Acetylcholine↗

The hypothalamic paraventricular nucleus mediates the photoperiodic control of reproduction but not the effects of light on the circadian rhythm of activity.

Photoperiods of less than 12.5 h of light/24 h induce gonadal regression in the golden hamster. Photic information is relayed from the retina to the hypothalamic suprachiasmatic nucleus (SCN), a structure responsible for the generation of many circadian rhythms including the circadian rhythms in locomotor activity and pineal melatonin synthesis and release. Although pineal melatonin mediates the photoperiodic-neuroendocrine response, the complete neural circuit from the SCN to the pineal gland is unknown. Complete destruction of the hypothalamic paraventricular nucleus (PVN) prevented short-day-induced testicular regression without affecting the circadian rhythm of locomotor activity. The results indicate that the PVN plays an important role in the photoperiodic-neuroendocrine circuit and is responsible for relaying information from the SCN to the pineal. A different efferent pathway connects the SCN to structures in the brain responsible for locomotor activity.

Animals↗

The suprachiasmatic nuclei: two circadian clocks?

Unilateral lesions of the bilaterally paired suprachiasmatic nuclei of the hypothalamus were made in golden hamsters maintained in constant light (LL). Prior to surgery, the circadian rhythm of locomotor activity had dissociated or 'split' into two distinct components in 19 out of 30 hamsters, while in the remaining 11 animals (i.e. non-splitters) a normal rhythm with a single bout of activity was maintained. Following destruction of a major portion (i.e. 50-100%) of a single suprachiasmatic nucleus (SCN) in 6 'split' and 5 'non-split' hamsters, a single circadian bout of activity was observed in all animals. In 9 of these 11 animals the circadian period of the activity rhythm was altered following unilateral SCN lesions. In two split animals sustaining lesions which missed the SCN, but disrupted efferents caudal to the SCN, the split condition was also abolished. Lesions which destroyed less than 50% of a single SCN did not abolish the split condition (n = 6) and had little effect on the circadian pattern of the non-splitters (n = 5). In contrast, bilateral destruction of the suprachiasmatic nuclei eliminated the circadian pattern of activity in both 'split' (n = 5) and 'non-split' (n = 1) animals. These results demonstrate that each SCN is capable by itself of maintaining circadian rhythmicity and that at least two circadian oscillators, or oscillating systems, reside within the suprachiasmatic nuclei.

Animals↗

Role for acetylcholine in mediating effects of light on reproduction.

The length of day, or photoperiod, regulates the annual cycle of reproductive activity in the golden hamster. The inhibitory effects of a short-day photoperiod on testicular function were prevented by nighttime, but not daytime, intraventricular injections of carbachol, a cholinergic agonist. Short pulses of light during the night also block short-day induced testicular regression. The findings suggest that acetylcholine may play an important role in the mechanism through which information about the light-dark environment is transferred to the hypothalamic-pituitary-gonadal axis.

Acetylcholine↗

Testosterone and photoperiod interact to regulate locomotor activity in male hamsters.

Testicular size, plasma testosterone levels, copulatory behavior, and daily locomotor activity are reduced in male hamsters after 10 weeks of exposure to short days. The role of testosterone in the short day-induced decline in locomotor activity was investigated, determining whether or not photoperiod could alter the effect of testosterone on activity. Castrated adult hamsters were allowed to acclimate to running wheels (wired to digital counters) and then were kept on either long (L:D 14:10) or short (L:D 6:18) days for 60 days. On Day 60, half of the animals on each light cycle were implanted with 12-mm-long testosterone-filled Silastic capsules; half received empty capsules. Digital counting of wheel-running activity continued for another 140 days. Blood samples taken on Day 200 confirmed L:D 14:10 and L:D 6:18 testosterone-treated hamsters had equivalent plasma testosterone levels. After an initial decline in activity, L:D 14:10 animals exhibited a progressive rise in mean running activity (from approximately 2000 to approximately 5000 wheel revolutions per day) through 100 days after the initiation of testosterone treatment. In contrast, activity levels in testosterone-treated L:D 6:18 animals remained uniform (approximately 2000 wheel revolutions per day) during this time, indicating exposure to short days rendered the hamsters less sensitive to the stimulatory effect of testosterone on activity. Of further interest was a marked increase in activity after 160-200 short days in animals treated with either testosterone-filled or empty capsules. It appears the total amount of daily locomotor activity in the hamster is modulated by circulating testosterone levels in a manner which is dependent upon the environmental photoperiod.

Animals↗