Biomedical subjects

F W Turek

Publications and source records attributed to F W Turek.

At least 91 records · Page 5Linked to original sources

PubMed1995

Aging alters the phase-resetting properties of a serotonin agonist on hamster circadian rhythmicity.

Serotonergic mechanisms are believed to play a considerable role in mediating the effects of photic and nonphotic stimuli on circadian rhythmicity. Because aging is associated with significant changes in the responsiveness of the rodent circadian system to major synchronizing agents in the environment, this study examined the phase-shifting effects of the 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin [8-OH-DPAT; 2.0, 5.0, and 8.0 mg/kg ip at circadian time 8 (CT 8)], on the 24-h activity rhythm of young (3-4 mo old) and old (18-19 mo old) golden hamsters. Aging was associated with a dramatic attenuation of the phase-shifting effects of 8-OH-DPAT in this species. The results suggest the existence of age-related deficits in the serotonergic control of mammalian circadian rhythmicity, which could interfere with the temporal adaptation of the senescent organism to its environment.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1995

Noradrenergic activity in rat brain during rapid eye movement sleep deprivation and rebound sleep.

Noradrenergic locus ceruleus neurons are most active during waking and least active during rapid eye movement (REM) sleep. We expected REM sleep deprivation (REMSD) to increase norepinephrine utilization and activate the tyrosine hydroxylase (TH) gene critical for norepinephrine production. Male Wistar rats were deprived of REM sleep with the platform method. Rats were decapitated after 8, 24, or 72 h on small (REMSD) or large (control) platforms or after 8 or 24 h of rebound sleep after 72 h of the platform treatment. During the first 24 h, norepinephrine concentration, measured by high-performance liquid chromatography/electrochemical detection, was lower in the neocortex, hippocampus, and posterior hypothalamus in REMSD rats than in large-platform controls. After 72 h of REMSD, TH mRNA, measured by in situ hybridization, was increased in the locus ceruleus and norepinephrine concentrations were increased. Polygraphy showed that small-platform treatment caused effective and selective REMSD. Serum corticosterone measurement by radioimmunoassay indicated that the differences found in norepinephrine and TH mRNA were not due to differences in stress between the treatments. The novel finding of sleep deprivation-specific increase in TH gene expression indicates an important mechanism of adjusting to sleep deprivation.

Animals↗

PubMed1994

Lesions of the thalamic intergeniculate leaflet block activity-induced phase shifts in the circadian activity rhythm of the golden hamster.

A variety of stimuli, which are associated with acute increases in locomotor activity, induce similar phase-dependent shifts in the circadian rhythm of locomotor activity in golden hamsters. Treatment with the benzodiazepine, triazolam (Tz), or transfer of an animal normally housed without a running wheel to a new cage with 1 h of access to a wheel are both examples of such stimuli. Phase shifts normally induced by injections of Tz can be blocked by lesions of the intergeniculate leaflet (IGL) of the thalamus. Experiments were conducted to determine whether phase shifts induced by transfer to a new cage with a running wheel also require an intact IGL. Animals normally housed without running wheels were transferred to new cages with access to wheels for 1 h a few hours before the expected onset of activity. They then received either lesions of the IGL or sham lesions and, after recovery, they were again transferred to new cages with running wheels for 1 h. Lesions of the IGL blocked phase shifts normally induced by wheel access while sham lesions had no effect. The amount of wheel-running and total locomotor activity which occurred during access to the running wheel were significantly reduced by IGL lesions. These results indicate that the phase-shifting effect of a novel running wheel depends upon an intact IGL.

Activity Cycles↗

PubMed1994

Mutagenesis and mapping of a mouse gene, Clock, essential for circadian behavior.

In a search for genes that regulate circadian rhythms in mammals, the progeny of mice treated with N-ethyl-N-nitrosourea (ENU) were screened for circadian clock mutations. A semidominant mutation, Clock, that lengthens circadian period and abolishes persistence of rhythmicity was identified. Clock segregated as a single gene that mapped to the midportion of mouse chromosome 5, a region syntenic to human chromosome 4. The power of ENU mutagenesis combined with the ability to clone murine genes by map position provides a generally applicable approach to study complex behavior in mammals.

Animals↗

PubMed1994

Grafting fetal suprachiasmatic nuclei in the hypothalamus of old hamsters restores responsiveness of the circadian clock to a phase shifting stimulus.

In the present study, 18-25-month-old hamsters free-running in constant dim light were injected, both before and after receiving fetal grafts containing either cerebellar tissue or the suprachiasmatic nuclei (SCN), with a dose of triazolam given at a time known to reliably phase shift the rhythm of locomotor activity in young hamsters. SCN-grafted animals, but not control animals implanted with fetal cerebellar tissue, showed a significantly greater response to the phase shifting effects of triazolam, demonstrating that at least some age-related changes in the circadian system can be reversed by neuronal transplantation. These results raise the possibility that neuropharmacological interventions that can simulate the effects of fetal SCN grafts might be useful in the treatment of age-related disorders in circadian function.

Aging↗

PubMed1994

Monoamine depletion blocks triazolam-induced phase advances of the circadian clock in hamsters.

Injections with the short-acting benzodiazepine, triazolam (Tz), 6 h before activity onset (CT6) produce large phase advances of the circadian pacemaker in hamsters. An increase in locomotor activity and/or the state of arousal is considered essential for the effects of Tz, suggesting the potential involvement of central monoaminergic systems in this process. The present study examines the effect of reserpine-induced monoamine depletion on the phase-shifting effects of Tz in hamsters. Wheel running activity of 16 male golden hamsters (14 weeks old) was continuously monitored in constant darkness. After a stable free-running circadian rhythm was established half of the animals received reserpine (2.5 mg/kg, s.c.) and the other half vehicle treatment. Ten days later all animals were given Tz injections (10 mg/kg i.p.) at CT6 and the circadian activity rhythm was monitored for 2 more weeks. An additional 10 animals were used to determine the effect of reserpine on the central monamine levels using high pressure liquid chromatography. A circadian rhythm of locomotor activity with reduced amplitude and longer free-running period persisted after reserpine treatment, despite the significant monoamine depletion. Triazolam injections at CT6 induced large phase-advances (93.1 +/- 14.9) in the control group that were markedly attenuated in 7 out of the 8 reserpine-treated animals (3.12 +/- 17.7 min, P < 0.01). Our results suggest that monoaminergic systems are essential for the phase-shifting effect of Tz upon the circadian system in hamsters.

Aging↗

PubMed1994

Circadian rhythms.

Changes in behavior which occur on a daily or circadian basis represent one of the most ubiquitous strategies by which most living organisms have adapted to their environment. Underlying the daily changes in behavior are a multitude of endocrine and metabolic rhythms which provide adaptively significant temporal organization within the organism. In mammals there appears to be a central circadian clock in the SCN which is responsible for generating and coordinating the entire 24-hour temporal organization of the animal. The circadian clock regulates the timing, duration, and characteristics of sleep, and together the circadian clock and sleep interact to control the timing of endocrine secretions. While the impact of disturbed endocrine circadian rhythms for the survival of the species has received very little attention, the almost universal presence of circadian rhythmicity within the endocrine system argues in support of the hypothesis that a disruption of the normal circadian organization within the endocrine system can have serious consequences for the health and well-being of the organism. It is particularly noteworthy that in advanced age, various alterations in circadian endocrine rhythms have been observed and these alterations may impair the ability of the animal to adapt normally to the environment. Relatively speaking, the study of circadian rhythms is a new field of biology, and as a result, much remains to be discovered about the physiological mechanisms that underlie rhythmicity, as well as the functional significance of 24-hour temporal organization for the survival of the species.

Activity Cycles↗

PubMed1994

Photoperiod regulates testis cell apoptosis in Djungarian hamsters.

Reproductive activity in the Djungarian hamster is controlled by seasonal variations in day length. Exposure to long days stimulates testis development, while exposure to short days induces testis regression. We recently found that testis regression after gonadotropin deprivation in rats is associated with increases in apoptosis. Here we sought to determine whether or not apoptosis is associated with the testis regression and/or recrudescence that occurs naturally in seasonally breeding mammals. Newborn male hamsters were maintained on long days (16L:8D) until 3 wk of age before being transferred to short days (8L:16D). Following decreases in serum FSH within 3 days of exposure to short days, testis weight decreased by 52% at Day 10, reaching a 70% decrease after 21 days. Analysis of testis cell DNA fragmentation showed a 4.9-fold increase of low-molecular-weight DNA as early as 5 days after transfer to short days; this was followed by a time-dependent decrease. The observed increases in testis cell apoptosis were correlated with decreases in serum testosterone, but decreases in Leydig cell LH receptor content were delayed. In a second study, 6-wk-old hamsters with regressed testes due to a 3-wk exposure to short days were transferred back to long days. After increases in serum FSH within 3 days of photostimulation, a 2-fold elevation in testis weight was found at Day 5. The increase in testis weight was associated with a 65% decrease of testis apoptosis within 5 days of photostimulation. Also, increases in serum testosterone and LH receptor content were observed after 5 and 10 days of exposure to long days, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Demonstration of rapid light-induced advances and delays of the human circadian clock using hormonal phase markers.

To determine the magnitude and direction of phase shifts of human circadian rhythms occurring within 1 day after a single exposure to bright light, plasma thyrotropin, melatonin, and cortisol levels and body temperature were monitored for 38 h in 17 men who were each studied two times, once during continuous dim light conditions and once with light exposure. After a period of entrainment to a fixed sleep-wake cycle, a 3-h light pulse (5,000 lux) was presented under constant routine conditions, and the resultant phase shifts were measured, also under constant routine conditions, on the 1st day after pulse presentation. The phase shifts in response to light occurred within 24 h and were in the delaying direction for most of the nocturnal period, with the crossover to phase advances occurring approximately 1 h after the temperature minimum. Phase shifts averaged 1 h, with delays being larger than advances, and were achieved without significant changes in rhythm amplitude. The immediate response of the human circadian clock to a single 3-h light pulse is thus characteristic of "type 1" resetting.

Adult↗

PubMed1994

Nocturnal exercise phase delays circadian rhythms of melatonin and thyrotropin secretion in normal men.

To determine whether a single episode of physical activity is capable of inducing rapid phase shifts in human circadian rhythms, 17 subjects were studied two times under constant routine conditions, once in the absence of stimulus and once with a 3-h nighttime pulse of exercise interrupting the constant routine conditions. The profiles of plasma cortisol, thyrotropin (TSH), and melatonin and of body temperature were monitored continuously to derive estimations of circadian phase position. The phase shifts were measured on the 1st day after exercise exposure. The timing of the exercise period ranged from -5 h to +4 h around the time of the minimum body temperature rhythm. Nighttime exercise was associated with 1- to 2-h phase delays of both the melatonin and TSH rhythms, with the size of the delays tending to be smaller when the exercise was presented in the latter part of the nighttime period and in the early morning. These data demonstrate that nonphotic stimuli may exert phase-shifting effects on the human circadian pacemaker.

Adult↗

PubMed1994

Effects of melatonin and time of day on in vitro pituitary gonadotropin basal secretion and GnRH responsiveness in the male golden hamster.

Melatonin, a pineal hormone, is known to play an important role in mediating changes in the reproductive system which occur in response to seasonal changes in the length of the day. An in vitro pituitary perifusion system has been used to examine both direct and indirect effects of melatonin on pituitary gonadotropin basal secretion and responsiveness to GnRH stimulation. Anterior pituitaries from adult male golden hamsters were perifused with an APS 10 perifusion system for 6 h. Both basal secretion and secretion in response to hourly GnRH stimulation (1 min, 35 ng/ml pulses) were evaluated for LH and FSH. In order to expose pituitaries to shorter and longer durations of melatonin, tissue was perifused with melatonin-containing medium following dissection in the daytime (when endogenous melatonin levels are low) and following dissection in the nighttime (when endogenous melatonin levels are high). Exposure of pituitary tissue from golden hamsters to melatonin during perifusion caused a decrease in basal secretion of LH but did not affect GnRH stimulated LH or FSH release regardless of the time of dissection. There was, however, an effect of some diurnal factor to lower FSH responsiveness to GnRH stimulation from tissue dissected in the nighttime. It is suggested that melatonin may be responsible for this diurnal difference. Therefore, melatonin can act directly at the anterior pituitary to lower basal LH secretion, and melatonin or some other diurnal factor can act in vivo to lower pituitary FSH secretion in response to GnRH stimulation during the night.

Animals↗

PubMed1994

Diurnal, photoperiodic, and age-related changes in plasma growth hormone levels in the golden hamster.

The golden hamster has been used extensively as an animal model for the study of both circadian and seasonal rhythms, and their regulation by the light-dark (LD) cycle. More recently, this species has been used to examine how the generation and entrainment of circadian rhythms are altered in advanced age. Recent studies in both humans and rodents indicate that age-related changes in the diurnal rhythm of pituitary growth hormone (GH) release may mediate some of the adverse effects of aging on a variety of physiological systems. As a first step in determining whether or not age-related changes in circulating GH levels are associated with changes in the regulation and/or expression of circadian rhythms, the effects of age on both the ultradian and diurnal patterns of plasma GH levels were determined in 3- to 22-month-old male hamsters that were bled every 15 min for a 24-hr period while entrained to an LD 14:10 light cycle. An additional study involving a similar blood collection protocol examined whether or not the length of the day is involved in the regulation of plasma GH levels. Although the frequency of pulsatile GH release did not change with advanced age, both the mean levels of GH per sample and the mean amplitude per pulse of GH were significantly elevated in 3- to 4-month-old animals, compared to animals that were 12-13, 15-16, or 21-22 months of age. In hamsters aged 3-4 and 12-13 months, there was an increase in both mean levels and the mean amplitude per pulse of GH, but not pulse frequency, during the night as compared to daytime values. No such diurnal rhythm was detected in the two groups of older animals. A clear diurnal rhythm in GH levels was also detected in animals maintained in a short-day (LD 6:18) cycle, and the mean levels of GH per sample were greater in hamsters maintained on short compared to long (LD 14:10) days. These results indicate that there are pronounced age-related changes in pituitary GH release in the hamster, and that both the time of day and the length of the day influence the pattern of GH release.

Aging↗

PubMed1994

Daily exposure to a nonphotic stimulus can alter photoperiodic response to short days in hamsters.

The ability of mammals to measure seasonal changes in daylength depends upon a circadian clock and the phase-relationship between this clock and the light: dark cycle. Recently, a number of pharmacological and nonpharmacological stimuli have been shown to have pronounced effects on the phase of the circadian clock of rodents. The objective of the present study was to determine if a drug-induced change in the phase-relationship between a measurable circadian rhythm (i.e., wheel running behavior) and the light:dark cycle would alter the effects of the light cycle on the neuroendocrine-gonadal axis. Adult male hamsters with regressed testes due to exposure to an inhibitory 10:14-hr light:dark cycle were daily injected with vehicle or the short-acting benzodiazepine, triazolam, while remaining on short days, while a control group of hamsters was transferred to a photostimulatory 14:10-hr light:dark cycle. Two other groups of hamsters with regressed testes were blinded and daily injected with vehicle or triazolam. The injections were timed to occur about 4 hr before activity onset because previous studies had demonstrated that injections of triazolam at this time can lead to a phase advance in the activity rhythm. The circadian rhythm of wheel running behavior was measured in all the animals maintained on the 10:14-hr light:dark cycle in order to monitor circadian phase. While no testicular growth was observed after 25 days of vehicle injections, growth was observed in the triazolam-treated animals that was comparable to that observed in control animals transferred to long days. Testicular growth in triazolam-treated animals was associated with an earlier onset of locomotor activity, when compared with the vehicle-treated animals. Importantly, triazolam had no effect on the testicular size of blind animals. These results indicate that daily injections of triazolam can stimulate neuroendocrine-gonadal activity by altering the phase-relationship between the cycle and the circadian clock involved in photoperiodic time measurement, and that agents which can affect the clock may be useful in altering seasonal cycles.

Animals↗

PubMed1994

Gene expression in a subpopulation of luteinizing hormone-releasing hormone (LHRH) neurons prior to the preovulatory gonadotropin surge.

Gene expression in luteinizing hormone-releasing hormone (LHRH) neurons was analyzed during the periovulatory period to (1) characterize temporal patterns of LHRH gene expression and their relationship(s) to gonadotropin surges, and (2) determine if any such changes are uniform or dissimilar at different rostrocaudal levels of the basal forebrain. The number of neurons expressing mRNA for the decapeptide, and the relative degree of expression per cell were analyzed using in situ hybridization and quantitative image analysis. Rats were killed at 1800 hr on metestrus (Met), 0800 hr, 1200 hr, 1800 hr, and 2200 hr on proestrus (Pro), or 0200 hr, 0800 hr, and 1800 hr on estrus (E; n = 5-6 rats/group). All sections were processed for LHRH mRNA in a single in situ hybridization assay. Sections were atlas matched and divided into four rostrocaudal groups for analysis: vertical limb of the diagonal band of Broca (DBB), rostral preoptic area/organum vasculosum of the lamina terminalis (rPOA/OVLT), medial preoptic area (mPOA), and suprachiasmatic/anterior hypothalamic area (SCN/AHA). Plasma LH and FSH levels from all animals were analyzed by RIA. The labeling intensity per cell was similar among all time points at all four rostrocaudal levels. The number of cells expressing LHRH mRNA, however, varied as a function of time of death during the estrous cycle, and this temporal pattern varied among the four anatomical regions. At the level of the mPOA, the number of cells was highest at 1200 hr on Pro, and then declined and remained low throughout the morning of E. At the level of the rPOA/OVLT, the greatest number of LHRH neurons was noted later in Pro, at 1800 hr, dropping rapidly to lowest numbers at 2200 hr. No significant changes in LHRH cell number occurred at the DBB or SCN/AHA levels. At all anatomical levels, the secondary surge of FSH was unaccompanied by any change in the number of neurons expressing LHRH mRNA. These data demonstrate that (1) the number of detectable LHRH mRNA-expressing cells fluctuates during the periovulatory period and (2) peak numbers of LHRH-expressing cells are attained in the mPOA before the onset of the LH surge and before peak LHRH cell numbers are seen at more rostral levels. A model is proposed in which gene expression in this subpopulation of LHRH neurons may be activated by preovulatory estrogen secretion and acutely reduced following the proestrous surge of progesterone.

Animals↗

PubMed1993

Fos protein expression in the circadian clock is not associated with phase shifts induced by a nonphotic stimulus, triazolam.

Recent studies have shown that light-induced phase shifts of the circadian rhythm of locomotor activity are associated with c-fos expression in the suprachiasmatic nucleus (SCN) and intergeniculate leaflet (IGL) of the lateral geniculate nucleus of rodents. In order to determine whether c-fos expression is necessary for the phase shifting effects of a non-photic stimulus, we assessed Fos-like immunoreactivity (Fos-lir) in the SCN and IGL at various times after an injection of the short-acting benzodiazepine, triazolam, at circadian time (CT) 6; i.e. at a time when triazolam induces an acute increase in locomotor activity and maximal phase advances in the circadian rhythm of locomotor activity. Specific Fos-lir staining was not observed in the SCN or IGL regions of any animals treated with triazolam or vehicle at any time point examined. These results indicate that exposure to an activity-inducing stimulus at circadian times when this stimulus induces phase shifts does not induce Fos protein synthesis in the SCN or IGL regions.

Amino Acid Sequence↗

PubMed1993

A cholinergic antagonist, mecamylamine, blocks light-induced fos immunoreactivity in specific regions of the hamster suprachiasmatic nucleus.

Recent studies have shown that light-induced phase shifts of the circadian rhythm of locomotor activity are associated with c-fos expression in the suprachiasmatic nucleus (SCN) of rodents. In order to explore further the importance of c-fos expression for the phase-shifting effects of light, we examined the effects of mecamylamine on light-induced Fos-like immunoreactivity (Fos-lir) in the SCN. Mecamylamine was chosen because it is a cholinergic antagonist that blocks the phase-shifting effects of light on the circadian activity rhythm in the golden hamster. Golden hamsters were entrained for at least 14 days to a 14 h light: 10 h dark photoperiod. Animals were then placed in constant darkness (DD) and during exposure to DD were subjected to one or more of the following treatments: (1) vehicle alone; (2) mecamylamine alone (450 micrograms, i.c.v.) at circadian time (CT) 19; (3) vehicle plus a light pulse at CT 19; (4) mecamylamine 10 min prior to the light pulse at CT 19. Mecamylamine blocked the phase-shifting effects of light on the circadian rhythm of locomotor activity when compared to vehicle-treated animals (P < 0.001). A light pulse at CT 19 induced Fos-lir in the SCN within 1 h, whereas treatment with vehicle or mecamylamine had no noticeable effect on Fos-lir in the SCN. Mecamylamine pretreatment dramatically reduced light-induced Fos-lir in the SCN by 75%. The most striking observation was the clear inhibition of Fos-lir by mecamylamine in the dorsomedial region of the SCN while there was little inhibition of Fos-lir in the most ventral portions of the SCN.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Monoamine depletion alters the entrainment and the response to light of the circadian activity rhythm in hamsters.

Reduced amplitude, shorter free-running periods and desynchronization among a number of circadian rhythms are associated with advanced age in rodents. The response of the hamster circadian system to photic stimuli is also altered during senescence. Decreased monoamine levels, receptor sites and neuronal populations are commonly observed in the aging brain. The objective of the present study was to determine if monoamine depletion with reserpine in young hamsters induces changes in the circadian rhythm of locomotor activity similar to those that occur spontaneously with aging. Wheel-running activity of 12 young hamsters under a 14 h-light/10 h-dark cycle was continuously monitored. The total activity level, the times of activity onset, peak and offset and the duration of activity were determined during a 1-week period after vehicle treatment and for three 1-week periods after reserpine treatment (4 mg/kg). A second group of eight reserpine-treated and six vehicle-treated animals was kept in constant darkness (DD). The period of the circadian activity rhythm in DD and the phase-shifts after short light pulses at circadian time 19 (CT19) were determined in the control and reserpine-treated groups. Brain monoamines in the hypothalamus, striatum and pons/medulla after reserpine and vehicle treatment were determined by high-pressure liquid chromatography. The data were analyzed with x2 periodogram and one-way ANOVA followed by Duncan's post hoc test. Reserpine treatment significantly reduced total wheel-running activity and the monoamine levels in the hypothalamus, striatum and pons/medulla.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1993

Aging alters the entraining effects of an activity-inducing stimulus on the circadian clock.

In young hamsters, a single injection of the short-acting benzodiazepine, triazolam, can induce permanent phase shifts in the circadian clock, while repeated injections of triazolam entrain the circadian clock to the period of the injections. Triazolam appears to act on the circadian clock by inducing an acute increase in the activity of the animals, which in turn phase-shifts the circadian clock. Surprisingly, single injections of benzodiazepines do not phase-shift the activity rhythm of old hamsters, despite the fact that such treatment induces similar acute changes in the activity state of young and old animals. We compared the entraining effects of repeated injections of triazolam on the circadian clock of young and old hamsters; while six out of seven young hamsters were entrained to the triazolam injections, only one out of seven old animals was entrained by this treatment. Three of the remaining six old hamsters showed a lengthening of the activity rhythm, while no consistent effect on the period of the activity rhythm was observed in the remaining three old animals. These results indicate that the circadian system of old hamsters becomes selectively unresponsive to synchronizing signals mediated by the activity-rest state, and suggest that aging is associated with a weakened coupling between the activity-rest cycle and the circadian clock.

Aging↗