Search PubMed⌕ Search

Biomedical subjects

F W Turek

Publications and source records attributed to F W Turek.

At least 19 recordsLinked to original sources
PubMed1999

Photoperiodic effects on gonadotropin-releasing hormone (GnRH) content and the GnRH-immunoreactive neuronal system of male Siberian hamsters.

Despite profound photoperiodic differences in circulating gonadotropin levels, consistent differences in the GnRH system have not been observed in Siberian hamsters (Phodopus sungorus) housed chronically in short or long days. During the transition from short to long days, however, male hamsters exhibit a transient increase in the number of cells expressing prepro-GnRH mRNA on the morning of the second long day. Here, we present two experiments designed to examine whether or not this change in mRNA level is associated with changes in GnRH protein synthesis. In the first experiment, we used RIA to measure GnRH content in preoptic area-mediobasal hypothalamic homogenates. We observed a significant increase in GnRH protein levels on the morning of the second long day relative to short- and long-day controls. The latter two groups did not differ from one another. In the second experiment, we used immunocytochemistry to quantify GnRH cell number in the various treatment groups. GnRH-immunoreactive (-ir) cell number did not increase significantly after long-day transfer relative to that in short-day controls; however, both of these groups had significantly more GnRH-ir neurons than long-day controls. We hypothesize that during the transition from short to long days, male Siberian hamsters experience a transient increase in GnRH production in a stable population of neurons. When GnRH secretion subsequently increases on long days, peptide content within neuronal cell bodies declines, leading to a decrease in the number of immunoreactive neurons detected. The rapid response of the hypothalamo-pituitary-gonadal axis in Siberian hamsters to a change in day length defines a narrow temporal window in which to identify the physiological, cellular, and molecular mechanisms mediating the photoperiodic regulation of reproduction.

Animals↗
PubMed1999

Circadian rhythms and depression: effects of exercise in an animal model.

There is a clear link between altered circadian rhythms and depressive disorders, although the nature of this relationship is unknown. In addition, exercise affects both mood and alters clock function. To investigate the relationship between circadian rhythms, depression, and exercise, 3-wk-old mice housed on a 12:12-h light-dark cycle were exposed to chronic stress (CS) for 6 wk before being placed into constant darkness (DD). One-half of both the control and stressed mice were given access to a running wheel. Stressed mice consumed significantly less of a 2% sucrose solution during CS and exhibited a significant increase in immobility in the forced swim test 3 wk after the termination of stress relative to control mice. These effects were more pronounced in mice without running wheels. Stressed mice also exhibited altered percent distribution of total activity and increased fragmentation of daily activity rhythms during CS relative to control mice. Alterations in percent distribution were more pronounced in animals without running wheels. No activity rhythm changes were seen in DD, and there were no differences in light-induced phase shifts between stressed and control mice. These results suggest that CS causes long-term depressive-like symptoms but does not have long-lasting effects on activity rhythms. These changes were more pronounced in mice without running wheels, suggesting that exercise may protect against the harmful effects of stress.

Activity Cycles↗
PubMed1998

Effects of aging on lens transmittance and retinal input to the suprachiasmatic nucleus in golden hamsters.

Old animals are less sensitive by almost an order of magnitude to the phase-shifting effects of a low intensity light pulse on the locomotor activity rhythm and the associated induction of immediate early genes in the circadian clock. The transmittance of energy from 200 to 700 nm through the excised lens of the eyes of young and old golden hamsters was measured to determine if an age-related difference exists in the transmittance of light. There is only a small decrease (8-50%) in transmittance, with the magnitude being dependent upon wavelength. No significant differences were detected between young and old animals in the retinal innervation of the suprachiasmatic nucleus (SCN). These results support the hypothesis that the observed decrease in sensitivity to light in the aged circadian system occurs within the SCN itself and/or retino-hypothalamic tract photoreceptors.

Aging↗
PubMed1998

Lesions of glucose-responsive neurons impair synchronizing effects of calorie restriction in mice.

Calorie restriction can induce phase-advances of daily rhythms in rodents exposed to light-dark cycles. To test whether glucose-responsive neurons are involved in the synchronizing effects of calorie restriction, C57BL/6J mice were injected with gold-thioglucose (GTG; 0.6 g/kg) which damages glucose-responsive neurons, primarily located in the ventromedial hypothalamus. From the day of injection, GTG-treated and control mice received a hypocaloric diet (66% of ad libitum food intake) 2 h after lights on. When mice were transferred to constant darkness after 4 weeks and fed ad libitum, the onset of circadian rhythm of locomotor activity was phase-advanced by 1 h in control but not in GTG-treated mice. Therefore, glucose-responsive neurons in the ventromedial hypothalamus may play a role in the synchronizing effects of calorie restriction on circadian rhythmicity.

Animals↗
PubMed1998

An NK1 receptor antagonist affects the circadian regulation of locomotor activity in golden hamsters.

Substance P (SP) is a neuromodulator which may participate in the photic regulation of the circadian timing system in mammals. The biological effects of SP are mediated by interaction with specific receptors, designated as NK1, NK2, and NK3. The NK1 subtype receptor is expressed in the circadian system. Experiment 1 was designed to test whether an NK1 antagonist mimics the effects of dark pulses. Hamsters were housed in constant lighting conditions, either constant darkness or constant light (around 250 lx), and they received an i.p. injection of either the specific NK1 receptor antagonist, L-760,735 (5 mg/kg), or saline during the mid-subjective day, a time when dark pulses cause a phase-advance in circadian rhythm of locomotor activity. After treatment with the NK1 antagonist, significant phase-advances of wheel-running activity rhythm were found in constant light, but not in constant darkness. Experiment 2 was designed to test the ability of the NK1 antagonist to block the phase-delaying and/or the phase-advancing effects of light in animals kept in constant darkness. Phase-advances of locomotor activity rhythm that can normally be induced by light pulses given during the late subjective night were markedly reduced by pre-treatment with the NK1 antagonist. By contrast, phase-delays that can be induced by lights pulses given during the early subjective night were unaffected by the NK1 antagonist. These data support the hypothesis that SP within the circadian system may, by interacting with NK1 receptors, modulate photic responses of the SCN pacemaker.

Animals↗
PubMed1998

Resynchronisation of a diurnal rodent circadian clock accelerated by a melatonin agonist.

Using 'jet lag' paradigms involving phase shifts in the light-dark (LD) cycle, we studied the effects of S-20098 on the circadian clock of a diurnal rodent. Arvicanthis mordax, entrained to a regular LD cycle, were subjected to advance shifts (i.e. 4, 6 or 8 h) in the LD cycle and injected with vehicle or the melatonin agonist S-20098 (20 mg/kg) the day of the shift (and also on subsequent days in the 6 h or 8 h shift paradigms). In each condition, S-20098 accelerated by about 30% resynchronization to the new LD cycle. These data, which are the first to demonstrate the chronobiotic effects of a melatonin agonist in a diurnal rodent, provide new insights for the design of human chronopharmacological protocols.

Acetamides↗
PubMed1998

Effects of gonadotropin-releasing hormone pulse frequency modulation on the reproductive axis of photoinhibited male Siberian hamsters.

In Siberian hamsters, photostimulation evokes differential release of the gonadotropins, with FSH rising rapidly and LH levels rising much later. We have tested the hypothesis that differential release of gonadotropins in this species can be mediated by changes in the frequency of pulsatile GnRH stimulation. Photoinhibited Siberian hamsters received GnRH pulses at frequencies of 1 pulse every 45 (fast), 90 (medium), or 180 min (slow). Animals were killed at 0, 3, 5, 10, 20, and 30 days after treatment. There was a clear GnRH pulse frequency effect on LH release, with fast pulses > medium pulses > slow pulses > short-day (SD) controls. In addition, 10 days of fast-frequency GnRH pulses produced LH levels significantly greater than LH levels in animals exposed to 10 days of medium or slow GnRH pulse frequencies. Pulsatile GnRH produced the following serum FSH relationships: medium pulses > fast pulses > SD. The FSH response to slow GnRH frequency fell between the two faster frequencies. The effect of GnRH pulse frequency on paired testes weight was as follows: fast pulses = medium pulses > slow pulses > SD controls. The differing GnRH pulse frequencies produced the following testosterone relationships; fast pulses > medium pulses = slow pulses = SD controls. These results agree with studies showing that slower GnRH pulse frequencies facilitate FSH release, while faster GnRH pulse frequencies favor LH release. Our observations are also consistent with the idea that the singular release of FSH after transfer of hamsters to a long-day photoperiod is mediated by alterations in the frequency of endogenous pulsatile GnRH release.

Animals↗
PubMed1998

Chronic circadian desynchronization decreases the survival of animals with cardiomyopathic heart disease.

Shift work is associated with increased cardiovascular morbidity and mortality. Whereas it has been suggested that continuous shifting of the circadian clock/sleep-wake cycle may have negative effects on health, there is very little experimental evidence to support such a hypothesis. Cardiomyopathic Syrian hamsters were either maintained on a fixed light-dark (LD) cycle (n = 31) or were subjected to a 12-h phase shift in the LD cycle on a weekly basis (n = 32). The duration of the life span was recorded for each animal. Chronic reversal of the external LD cycle at weekly intervals resulted in a significant decrease in the survival time in cardiomyopathic hamsters with the median life span being reduced by 11%. Disrupting normal circadian rhythmicity in an animal susceptible to early mortality due to cardiac disease results in a further decrease in longevity. The deleterious effects of the chronic phase shifts in the LD cycle in cardiomyopathic hamsters may be related to reports of increased cardiovascular morbidity and mortality in humans engaged in shift work.

Animals↗
PubMed1998

Effects of bright light on age-related changes in the locomotor activity of Syrian hamsters.

Syrian hamsters display age-related changes in the expression of circadian rhythms and in responsiveness of the circadian system to photic and non-photic stimuli. This study characterized the effects of age on the locomotor activity rhythm of middle-aged and old hamsters and evaluated the effects of strengthening the entraining light signal. Compared with young (4.5 mo) animals, middle-aged (11.25 mo) and old (16 mo) animals displayed increased daily bouts of activity (P < 0.001) and reduced total daily activity and activity rhythm amplitude (P < 0.05) in 14:10-h light-dark cycles. After the light intensity was increased from 300 to 1,500 lx during the light cycle, middle-aged hamsters demonstrated decreased daily activity bouts (P < 0.05) and increased total daily activity (P < or = 0.01) and activity rhythm amplitude (P < or = 0.001) compared with controls maintained in 300 lx. The pattern of changes in the activity rhythm of old experimental animals was similar to trends observed in middle-aged experimental hamsters, although not as robust. Thus age-related changes in the activity rhythm are occurring by middle age in hamsters, and the provision of stronger entraining signals may lead to more stable circadian organization.

Aging↗
PubMed1998

Entrainment in calorie-restricted mice: conflicting zeitgebers and free-running conditions.

Phase-shifting effects of timed calorie restriction were investigated in mice during exposure to a 12:12-h light-dark cycle. Food-anticipatory activity (FAA), the output of a food-entrainable pacemaker, was expressed before the time of feeding whether mice received daily hypocaloric food (3.3 g of chow/day) or normocaloric food (5 g of chow/day) at zeitgeber time (ZT) 2 (ZT12 = lights off). Subsequently, mice were placed in constant darkness and fed ad libitum. The onset of the nocturnal period of locomotor activity was phase advanced by 1 h in calorie-restricted mice compared with normocalorie-fed controls. The phase advance still occurred when FAA was prevented by restraining calorie-restricted mice. Giving hypocaloric food at ZT2, ZT10, ZT14, or ZT22 phase advanced the nocturnal pattern of activity by 1, 3, 1, and 1 h, respectively. After transfer to constant darkness, FAA free ran in parallel with the normal nocturnal period of locomotor activity. A light pulse during the early subjective night phase delayed both components. These results indicate that 1) timed calorie restriction under a light-dark cycle can phase advance the light-entrainable pacemaker with a phase-dependent magnitude, 2) FAA feedback is not crucial for the observed phase advance, and 3) the light-entrainable pacemaker may control the period of the food-entrainable pacemaker in mice fed ad libitum.

Animals↗
PubMed1998

Circadian rhythms.

1997 marks the 25th anniversary of the discovery of the master circadian pacemaker in mammals in the hypothalamic suprachiasmatic nucleus. Remarkable progress has been made over the last 25 years in elucidating the physiological mechanisms involved in the entrainment, generation and expression of circadian rhythms at the cellular and systems levels. The recent discovery and cloning of the first mammalian clock gene is expected to lead to rapid advances in the understanding of the genetic and molecular mechanisms underlying circadian rhythmicity in mammals. Indeed, the impressive and extensive database on circadian rhythms in mammals obtained over the past 25 years provides a foundation for making rapid progress in utilizing future genetic and molecular findings for discovering the fundamental mechanisms controlling 24-hour temporal organization.

Animals↗
PubMed1998

Roles of suprachiasmatic nuclei and intergeniculate leaflets in mediating the phase-shifting effects of a serotonergic agonist and their photic modulation during subjective day.

Serotonin (5-HT) has been implicated in the phase adjustment of the circadian system during the subjective day in response to nonphotic stimuli. Two components of the circadian system, the suprachiasmatic nucleus (SCN) (site of the circadian clock) and the intergeniculate leaflet (IGL), receive serotonergic projections from the median raphe nucleus and the dorsal raphe nucleus, respectively. Experiment 1, performed in golden hamsters housed in constant darkness, compared the effects of bilateral microinjections of the 5-HT1A/7 receptor agonist, 8-hydroxydipropylaminotetralin (8-OH-DPAT; 0.5 microgram in 0.2 microliter saline per side), into the IGL or the SCN during the mid-subjective day. Bilateral 8-OH-DPAT injections into either the SCN or the IGL led to significant phase advances of the circadian rhythm of wheel-running activity (p < .001). The phase advances following 8-OH-DPAT injections in the IGL were dose department (p < .001). Because a light pulse administered during the middle of the subjective day can attenuate the phase-resetting effect of a systemic injection of 8-OH-DPAT, Experiment 2 was designed to determine whether light could modulate 5-HT agonist activity at the level of the SCN and/or the IGL. Serotonergic receptor activation within the SCN, followed by a pulse of light (300 lux of white light lasting 30 min), still induced phase advances. In contrast, the effect of serotonergic stimulation within the IGL was blocked by a light pulse. These results indicate that the respective 5-HT projections to the SCN and IGL subserve different functions in the circadian responses to photic and nonphotic stimuli.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1997

Comparative effects of a melatonin agonist on the circadian system in mice and Syrian hamsters.

S-20098 has potent and specific agonist properties on melatonin receptors both in vitro and in vivo. Behavioral studies on rodents already showed that repeated intraperitoneal administration of S-20098 could dose-dependently alter the functioning of the circadian clock. To determine whether single administration of S-20098 could alter the circadian rhythms of rodents, we first used the phase-response curve (PRC) approach in two different species: Syrian hamsters and mice (C3H/HeJ). Our results show that the shape, circadian times and extent of the PRC to S-20098 look very similar in mice and hamsters. In both species, the phase advance portion of the PRC to S-20098 is limited to a 3 h window preceding the onset of locomotor activity, but the magnitude of phase shifts is larger in mice. We also tested the phase shifting effects of increasing doses of S-20098 during the interval of maximal sensitivity to this compound. Treatment with S-20098 induces dose-dependent phase shifts, with maximal shifts observed after injections of 20 and 25 mg/kg S-20098 i.p., respectively, in mice and hamsters. Those results are in agreement with the limited distribution of melatonin-binding sites within the circadian clock of adult Syrian hamsters, as compared to other rodents.

Acetamides↗
PubMed1997

Positional cloning of the mouse circadian clock gene.

We used positional cloning to identify the circadian Clock gene in mice. Clock is a large transcription unit with 24 exons spanning approximately 100,000 bp of DNA from which transcript classes of 7.5 and approximately 10 kb arise. Clock encodes a novel member of the bHLH-PAS family of transcription factors. In the Clock mutant allele, an A-->T nucleotide transversion in a splice donor site causes exon skipping and deletion of 51 amino acids in the CLOCK protein. Clock is a unique gene with known circadian function and with features predicting DNA binding, protein dimerization, and activation domains. CLOCK represents the second example of a PAS domain-containing clock protein (besides Drosophila PERIOD), which suggests that this motif may define an evolutionarily conserved feature of the circadian clock mechanism.

Amino Acid Sequence↗
PubMed1997

The mouse Clock mutation behaves as an antimorph and maps within the W19H deletion, distal of Kit.

Clock is a semidominant mutation identified from an N-ethyl-N-nitrosourea mutagenesis screen in mice. Mice carrying the Clock mutation exhibit abnormalities of circadian behavior, including lengthening of endogenous period and loss of rhythmicity. To identify the gene affected by this mutation, we have generated a high-resolution genetic map (> 1800 meioses) of the Clock locus. We report that Clock is 0.7 cM distal of Kit on mouse chromosome 5. Mapping shows that Clock lies within the W19H deletion. Complementation analysis of different Clock and W19H compound genotypes indicates that the Clock mutation behaves as an antimorph. This antimorphic behavior of Clock strongly argues that Clock defines a gene centrally involved in the mammalian circadian system.

Animals↗
PubMed1997

Age-related changes in the photoperiodic response of Siberian hamsters.

Previous studies indicate that as Siberian hamsters (Phodopus sungorus) age, they may lose their ability to show gonadal regression in response to short days. In one study, hamsters that regressed on short days early in life failed to regress when exposed to short days a second time later in life. Thus, Siberian hamsters may experience age-related deficits in photoresponsiveness or may be incapable of regressing twice. In the present study, we attempted to discriminate between these possibilities by examining patterns of gonadal regression in hamsters transferred back and forth from long (16L:8D) to short days (6L:18D) every 6.5, 13, or 26 wk for a 2-yr period. A control group was maintained on long days and had enlarged gonads throughout the entire study. Hamsters alternating between 26 wk of long and short days exhibited complete gonadal regression during their initial but not during their second exposure to short days. Hamsters alternated between long and short days every 13 or 6.5 wk showed regression two to three times, respectively. After about 52 wk of age, the majority of animals in both groups did not regress when exposed to short days. Taken together, the results of this experiment indicate that male Siberian hamsters 1) can exhibit at least two rounds of short-day-induced gonadal regression and 2) fail to regress on short days after about 1 yr of age.

Aging↗
PubMed1997

Roles of intensity and duration of nocturnal exercise in causing phase delays of human circadian rhythms.

To determine the roles of intensity and duration of nocturnal physical activity in causing rapid phase shifts of human circadian rhythms, eight healthy men were studied three times under constant conditions with no exercise, a 3-h bout of moderate-intensity exercise, or a 1-h bout of high-intensity exercise. Exercise stimulus was centered at 0100. Circadian phase was estimated from the onsets of the nocturnal elevation of plasma thyrotropin (TSH) and melatonin. Mean phase shifts of TSH onsets were -18 +/- 8 (baseline), -78 +/- 10 (low-intensity exercise, P < 0.01), and -95 +/- 19 min (high-intensity exercise, P < 0.01). Mean phase delays of melatonin onsets were -23 +/- 10 (baseline), -63 +/- 8 (low-intensity exercise, P < 0.04), and -55 +/- 15 min (high-intensity exercise, P < 0.12). Taken together with our previous findings, this study indicates that nocturnal physical activity may phase delay human circadian rhythms and demonstrates that phase-shifting effects may be determined with exercise durations and intensities compatible with the demands of a real-life setting.

Adult↗