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F W Turek

Publications and source records attributed to F W Turek.

At least 73 records · Page 4Linked to original sources
PubMed1997

Effects of aging on the circadian rhythm of wheel-running activity in C57BL/6 mice.

The effects of age on the circadian clock system have been extensively studied, mainly in two rodent species, the laboratory rat and the golden hamster. However, less information is available on how aging alters circadian rhythmicity in a commonly studied rodent animal model, the mouse. Therefore, in the present study we compared the rhythm of wheel-running activity in adult (6-9 mo) and old (19-22 mo) C57BL/6J mice maintained under different lighting conditions for a period of 4 mo. During this period, mice were subjected to phase advances and phase delays of the light-dark (LD) cycle and eventually to constant darkness (DD). In LD (12 h light, 12 h dark), old mice exhibited delayed activity onset relative to light offset and an increase in the variability of activity onset compared with adult mice. After a 4-h phase advance of the LD cycle, old mice took significantly longer to reentrain their activity rhythm when compared with adult animals. Old mice also demonstrated a decline in the number of wheel revolutions per day and a tendency toward a decrease in the length of the active phase. An increase in fragmentation of activity across the 24-h day was obvious in aging animals, with bouts of activity being shorter and longer rest periods intervening between them. No age difference was detected in the maximum intensity of wheel-running activity. In DD, the free-running period was significantly longer in old mice compared with adults. In view of the rapidly expanding importance of the laboratory mouse for molecular and genetic studies of the mammalian nervous system, the present results provide a basis at the phenotypic level to begin to apply genetic methods to the analysis of circadian rhythms and aging in mammals.

Aging↗
PubMed1997

Rapid photoperiod-induced increase in detectable GnRH mRNA-containing cells in Siberian hamster.

To determine whether changes in gonadotropin-releasing hormone (GnRH) neurons are early indicators of photostimulation, Siberian hamsters were placed in short days (6:18-h light-dark) at 3 (experiment 1) or 6 (experiment 2) wk of age where they were held for 3 (experiment 1) or 4 (experiment 2) wk. Hamsters were then moved to long photoperiod (16:8-h light-dark). In experiment 1, brains were collected 1-21 days after transfer from short to long days. In experiment 2, brains were collected only on the second morning of long day exposure. Long and short day controls were included in both experiments. Cells containing GnRH mRNA, as visualized by in situ hybridization, were counted. As expected, there were no differences in the number of detectable GnRH mRNA-containing cells among animals chronically exposed to long or short photoperiods. However, on the second morning after transfer from short to long photoperiod, a positive shift in the distribution of GnRH mRNA-containing cells occurred relative to the respective controls in the two experiments. Increases in follicle-stimulating hormone secretion and gonadal growth occurred days later. In conclusion, a rapid but transient increase in the distribution of detectable GnRH mRNA-containing cells is an early step in the photostimulation of the hypothalamic-pituitary-gonadal axis.

Animals↗
PubMed1997

Quantitative analysis of the age-related fragmentation of hamster 24-h activity rhythms.

The continuous monitoring of spontaneous locomotor activity has emerged as one of the most widely used metrics in rodent circadian research. This behavioral measure is also extremely useful for the description of the effects of aging on circadian rhythms. The present study describes the successful use of a log-survivorship approach to identify discrete bouts of hamster wheel-running activity and provides a detailed description of the age-related fragmentation in the 24-h profile of this behavioral variable. In addition, stepwise discriminant analysis identified the most important quantitative measures for distinguishing between the individual patterns of wheel-running activity of young (3 mo) and old (17-18 mo) golden hamsters. The results suggest that this method of bout analysis can be a valuable tool for the study of genetic, developmental, neurochemical, physiological, and environmental factors involved in the temporal control of rodent locomotor behavior.

Aging↗
PubMed1997

Neonatal hypothyroidism permanently alters follicle-stimulating hormone and luteinizing hormone production in the male rat.

Transient neonatal hypothyroidism, induced with the goitrogen 6-n-propyl-2-thiouracil (PTU), results in dramatic increases in both testis size and sperm production in the adult rat. The observed increases in testis size and function occur in the presence of normal circulating testosterone levels. However, circulating gonadotropin levels are chronically reduced by 30-50% at all times in treated males. To better understand the permanent reduction in serum gonadotropin levels following transient neonatal hypothyroidism, we conducted a series of experiments to evaluate pituitary and hypothalamic function in the adult male PTU-treated rat. PTU treatment led to a significant reduction in GnRH-stimulated LH production. Castration resulted in 3.9- to 8.5-fold increases in circulating gonadotropin levels in both treated and control males; however, the absolute increases were significantly reduced in treated males. In contrast to circulating levels, pituitary gonadotropin contents did not increase in treated males after castration. PTU treatment did not lead to a reduction in the density of either luteotropes or folliculotropes, and both cell types increased in size and density after castration. The relative concentrations of both gonadotropin beta-subunit messenger RNAs increased more slowly in treated males than in controls after castration. Thus, although treated rats have the intrinsic ability to produce normal circulating levels of LH and FSH, gonadal feedback and an overall reduction in gonadotrope synthetic ability combine to produce the chronically reduced circulating levels of these hormones.

Animals↗
PubMed1996

Critical period for cycloheximide blockade of light-induced phase advances of the circadian locomotor activity rhythm in golden hamsters.

Recent studies indicate that the protein products of genes involved in transcriptional regulation play an important role in light-induced phase-shifting of the circadian clock, and suggest that protein synthesis may be necessary for some critical steps in the process by which light can induce a phase shift. In order to determine if this protein-dependent step occurs before, during or at some time after the light pulse is presented, golden hamsters were treated with the protein synthesis inhibitor, cycloheximide (65 mg/kg, injected subcutaneously), at various times relative to the presentation of a light pulse that normally induces an advance in the circadian locomotor activity rhythm. When hamsters were treated with cycloheximide 1 h or 30 min before, as well as 0, 1, 2, 3 or 4 h after the onset of the light pulse; the phase advancing effects of light were completely blocked and delay phase shifts were observed. The observed phase shifts in these groups of animals were not significantly different from those observed in animals treated with cycloheximide without exposure to light. Treatment with cycloheximide 6 or 3 h before the light pulse partially blocked light-induced phase advances. The phase advancing effects of light were not altered in those animals injected with cycloheximide 6 or 9 h after the light pulse. These results support the hypothesis that protein synthesis is necessary for light-induced phase advances in the mammalian circadian clock, and indicate that such synthesis is necessary for at least 4 h after the light pulse for phase shifts to occur. Thus, light may not induce an instantaneous (< 1 h) phase shift in the circadian clock of hamsters, but instead depends on the synthesis of proteins for about 4 h after light stimulation.

Animals↗
PubMed1996

Quantitative differences in the circadian rhythm of locomotor activity and vasopressin and vasoactive intestinal peptide gene expression in the suprachiasmatic nucleus of tau mutant compared to wildtype hamsters.

The activity profiles of homozygous tau mutant hamsters bred in our colony exhibit several differences when compared to wildtype golden hamsters. In addition, tau mutant hamsters respond to saturating white light pulses presented between circadian time (CT) 11 and CT 16 with extremely large phase shifts (type 0 resetting) after prolonged time in constant darkness. We measured five parameters of the activity rhythm early during exposure to constant darkness (DD) (cycles 5-9), and after 44-48 cycles in DD, and we confirmed the tau mutants' unusual phase shifting response to light. Next we determined whether neurotransmitter peptide mRNA levels in the SCN differed between wildtype and tau mutant hamsters exhibiting these divergent activity patterns and responses to light. After 49 circadian cycles in DD, tau mutant hamsters responded to a 1 h light pulse at CT 15 with phase shifts averaging 10.19 +/- 0.35 h. Among wildtype hamsters the mean phase shift was 1.22 +/- 0.34 h and the largest phase shift observed was 3.67 h. Total wheel revolutions/circadian cycle were significantly lower in tau mutants (4022 +/- 1103) vs. wildtypes (7528 +/- 458) and there was a significant decrease in wheel-running activity after prolonged exposure to DD, particularly among the wildtype hamsters (tau = 3045 +/- 972, wildtype = 4362 +/- 388 rev/circadian cycle). When analyzed by 5 min segments throughout the circadian cycle, the highest intensity wheel-running activity did not differ between groups and there was no significant effect of length of time in DD on this measure (tau = 38.5 +/- 6.3 and 38.4 +/- 4.7 rev/min, wildtype = 46.8 +/- 1.7 and 41.4 +/- 2.7 rev/min early or late in DD, respectively). The precision of activity onset differed greatly between groups with tau mutants exhibiting a much higher daily deviation from mean tau (1.00 +/- 0.24 h) than wildtypes (0.14 +/- .02 h). Activity onset became significantly less precise with increased time in DD: tau = 1.66 +/- 0.21 h, wildtype = 0.45 +/- 0.14 h after 44-48 circadian cycles. The length of the active period, alpha, was significantly shorter in tau mutants than in wildtypes (7.2 +/- 0.2 h vs. 8.0 +/- 0.2 h) but alpha was a similar percentage of tau in the two groups (tau mutant = 36%, wildtype = 33%). After 48 circadian cycles in DD, alpha measured 7.2 +/- 0.5 h in tau mutants and 8.9 +/- 0.6 h in wildtypes, thus there was no significant effect of time in DD on this parameter. Activity records of tau mutant animals appear more fragmented to the eye and we quantitated this with a computer-aided analysis of the number of bouts of wheel-running per active period. Wildtype hamsters exhibited 2.8 +/- 0.2 bouts of wheel-running activity early in DD and 3.1 +/- 0.2 bouts per circadian cycle later in DD. The activity records of tau mutant hamsters were significantly more fragmented but this group actually showed some consolidation of bouts per circadian cycle after prolonged time in DD (4.7 +/- 0.3 vs. 3.9 +/- 0.3 bouts per cycle). Wildtype and tau mutant hamsters were killed after 66-71 cycles in DD at either CT 4 or CT 16 and in situ hybridization was performed for vasopressin (AVP) and vasoactive intestinal peptide (VIP). Levels of AVP and VIP mRNA were significantly lower in tau mutant than wildtype hamsters at CT 16. We conclude that the tau mutation causes these differences in gene expression and we speculate that differences in the peptidergic output of the clock may have some relevance for the differences in the quantitative aspects of the activity rhythm and the response to light pulses exhibited by these animals.

Animals↗
PubMed1996

Phase-shifting effects of a serotonin agonist in tau mutant hamsters.

Previous studies indicate that the advance region of the tau mutant hamster's phase-response curve (PRC) to non-photic stimuli, such as NPY and wheel pulses, is characterized by earlier timing and increased amplitude in comparison with that of wild-type animals. Since, recent evidence suggests that serotonergic pathways may play an important role for the non-photic phase resetting of the rodent circadian pacemaker, PRCs to the serotonin (5-HT) agonist, 8-OH-DPAT (5 mg/kg i.p), were generated in both wild-type and tau mutant hamsters kept in constant darkness. The results indicate that the tau mutation is associated with changes in the timing, but not the amplitude of the advance region of the PRC to 8-OH-DPAT and suggest that serotonergic agents and other non-photic or activity-inducing stimuli may share some common mechanisms for resetting the phase of the rodent circadian pacemaker.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1996

Melatonin hype hard to swallow.

Melatonin is being touted as the latest cure-all. But in their eagerness to explain to the public the possible health benefits of this natural hormone, the mass media as well as some scientists have misrepresented the scientific data.

Animals↗
PubMed1996

Effects of aging on light-induced phase-shifting of circadian behavioral rhythms, fos expression and CREB phosphorylation in the hamster suprachiasmatic nucleus.

Aging is associated with a variety of alterations in circadian rhythms, including changes in the response to environmental stimuli. The underlying causes for these age-related changes in the circadian system remain unknown. Recent studies have demonstrated that light induces the expression of Fos and phosphorylation of the cyclic-AMP response element-binding protein in the rodent suprachiasmatic nuclei, the location of a master circadian pacemaker in mammals, suggesting that these transcription factors may mediate the effects of light on the circadian clock. The purpose of this study was to determine the effects of aging upon light-induced phase-shifting of circadian locomotor activity rhythms, Fos protein expression and cyclic-AMP response element-binding protein phosphorylation in the suprachiasmatic nuclei. Young (three to four months) and old (18-22 months) male golden hamsters free-running in constant darkness were exposed to 5-min monochromatic light pulses of different irradiance levels, at circadian time 19, after which either steady-state phase shifts of locomotor activity rhythms were measured, or else immunocytochemistry for Fos or for phospho-cyclic-AMP response element-binding protein was performed. Old hamsters were approximately 20 times less sensitive to the phase-shifting effects of light on the activity rhythm, and the photic irradiance threshold for Fos-like immunoreactivity induction in the suprachiasmatic nuclei was elevated when compared to young animals. Aging was also associated with a deficit in cyclic-AMP response element-binding protein phosphorylation by light. These data indicate that there are dramatic changes in light-activated molecular responses in the suprachiasmatic nuclei of old hamsters, and suggest that these molecular changes may underlie age-related changes in the effects of light on the circadian clock system.

Age Factors↗
PubMed1996

The effect of REM sleep deprivation on somatostatin and growth hormone-releasing hormone gene expression in the rat hypothalamus.

Growth hormone-releasing hormone (GHRH) and somatostatin (SRIF) have been implicated as sleep factors. We studied how the hypothalamic SRIF/GHRH system is affected by possible feedback regulation resulting from REM sleep deprivation at the level of gene expression and how this is reflected in serum growth hormone (GH) content. Male rats were deprived of REM sleep on small platforms for 24 or 72 h, and one group was allowed a rebound sleep of 24 h after 72 h deprivation. Animals maintained on large platforms and animals taken directly from their home cages served as controls. In situ hybridization was made from 20 microm cryosections through the periventricular, paraventricular and arcuate hypothalamic nuclei using oligonucleotide probes for GHRH and SRIF. The number of cells expressing SRIF or GHRH was counted. Serum GH was measured by means of radioimmunoassay in similarly treated rats. Fewer cells expressed GHRH in the paraventricular nucleus of animals subjected to 24 and 72 h of REM sleep deprivation than in home control animals. A similar trend was observed in the arcuate nucleus. The number of cells expressing SRIF was elevated in the arcuate nucleus after 24 h of REM sleep deprivation but not after 72 h. In the periventricular nucleus the number of cells expressing SRIF was higher after 72 h of deprivation when compared to expression in animals maintained on large platforms. Serum GH levels were decreased in animals maintained on either small or large platforms. It is concluded that the expression of the SRIF and GHRH genes is modulated by REM sleep deprivation.

Animals↗
PubMed1995

A serotonin neurotoxin attenuates the phase-shifting effects of triazolam on the circadian clock in hamsters.

Several lines of evidence suggest the potential involvement of serotonergic pathways in mediating the effects of activity-inducing stimuli on the circadian clock in rodents. The aim of the present 3 experiments was to examine the effects of the serotonergic neurotoxin, p-chloroamphetamine (PCA, 10 mg/kg) on: (1) the monoamine levels of the hypothalamus, frontal cortex and hippocampus in the hamster; (2) the phase shifts in the circadian rhythm of locomotor activity of hamsters in response to treatment with the short-acting benzodiazepine, triazolam (7.5 mg/kg); and (3) the magnitude of the acute increase in locomotor activity associated with triazolam administration in this species. The administration of PCA to hamsters caused changes of specific monoaminergic systems in the hypothalamus, that were limited to a selective decrease in serotonin levels 7 days post-treatment. The phase shifts of the circadian clock in response to triazolam treatment at CT 6 were considerably attenuated following the administration of the 5-HT neurotoxin. The total amount and the profiles of triazolam-induced wheel-running and general cage activity between CT 6 and CT 12 were not significantly affected by the PCA treatment. The finding that a 5-HT neurotoxin can attenuate the phase-shifting effects of triazolam in hamsters, without interfering with its activity-inducing properties, suggests that serotonergic afferents might be involved in the mechanism for non-photic phase-shifting of the circadian system.

Animals↗
PubMed1995

REM sleep deprivation induces galanin gene expression in the rat brain.

Rats were deprived of REM sleep for 24 h by keeping them on small platforms that were placed in a water bath (the platform method). Galanin coding mRNA was visualized using in situ hybridization, and cells expressing galanin mRNA were counted. In REM sleep-deprived animals the cell count was higher in the preoptic area and periventricular nucleus. Lesions of this area have been reported to induce wakefulness in cats and rats. Galanin administered into the lateral ventricle had no effect on sleep. We conclude that REM sleep deprivation can induce galanin gene expression in some brain areas, but galanin alone does not modify spontaneous sleep.

Animals↗
PubMed1995

Alterations in the circadian system in advanced age.

In addition to light, a variety of non-photic stimuli can induce phase shifts in the circadian clock of rodents. We have examined the effects of advanced age on the response of the circadian clock to both photic and non-photic stimuli in old hamsters (i.e., over 16 months of age). Among the age-related changes in the circadian rhythm of locomotor activity are: (1) alterations in the phase angle of entrainment to the light-dark cycle; (2) an altered response to the phase-shifting effects of light pulses; (3) changes in the time it takes to re-entrain to a new light-dark cycle; and (4) a loss of responsiveness to the phase-shifting or entraining effects of stimuli which induce an acute increase of activity. Many of the effects of ageing on the circadian clock system can be simulated in young animals by depleting brain monoamine levels, suggesting that ageing alters monoaminergic inputs to the clock. Some of the age-related changes in the response of the clock to an activity-inducing stimulus can be reversed by implanting old animals with fetal suprachiasmatic nuclear tissue. Determining the physiological basis of age-related changes in the responsiveness of the clock to both internal and external stimuli, and the mechanisms by which normal circadian functioning can be restored, should lead to new insight into the functioning of the circadian clock and may suggest new approaches to the normalization of disturbed circadian rhythms.

Aging↗
PubMed1995

Pharmacological and genetic approaches for the study of circadian rhythms in mammals.

Two different approaches have been utilized to study the controlling mechanisms that underlie the generation and entrainment of circadian rhythms in mammals. The use of specific drugs to alter the period and/or the phase of circadian rhythms has provided new insights into both the pathways by which environmental information reaches the mammalian circadian pacemaker in the suprachiasmatic nuclei (SCN) and the cellular and neurochemical events within the SCN itself which are involved in circadian rhythmicity. A second approach, which seeks to exploit genetic differences in the properties of the circadian system, holds the promise of eventually defining the cellular and molecular events that are part of the clock itself, the events that underlie the entrainment of the circadian clock by environmental factors, and the expression of overt rhythms driven by the clock. It is anticipated that the pharmacological and genetic approaches to the study of circadian rhythms will complement each other as the underlying physiological mechanisms of the circadian clock system become defined.

Afferent Pathways↗
PubMed1995

Effects of age on the circadian system.

While aging has been associated with changes in the period and amplitude of circadian rhythms, little is known about how aging influences the response of the circadian clock to environmental stimuli. In this paper, we report on recent studies designed to determine the effects of advanced age on the response of the circadian clock to both photic and nonphotic stimuli in old hamsters (e.g., over 16 mo of age). Among the most pronounced age-related changes in the circadian rhythm of locomotor activity are: (a) alterations in the phase-angle of entrainment to the light-dark cycle; (b) an increase in the magnitude of phase shifts induced by pulses of light presented at specific circadian times; and (c) a loss of responsiveness to the phase shifting or entraining effects of stimuli which induce an acute increase of activity. Depletion of brain monoamine levels in young animals can induce changes in the responsiveness of the circadian clock to environmental stimuli which are similar to those which occur spontaneously in old animals, suggesting that aging alters monoaminergic inputs to the clock. Some of the age-related changes in the response of the clock to an activity-inducing stimulus can be reversed by implanting old animals with fetal SCN tissue. Determining the physiological basis for age related changes in the responsiveness of the clock to both internal and external stimuli, and the mechanisms by which normal circadian function can be restored, should lead to new insight into the functioning of the circadian clock and may lead to new approaches for normalizing disturbed circadian rhythms.

Aging↗
PubMed1995

Blockade of singular follicle-stimulating hormone secretion and testicular development in photostimulated Djungarian hamsters (Phodopus sungorus) by a gonadotropin-releasing hormone antagonist.

Photostimulated male Djungarian hamsters following placement in a long-day photoperiod exhibit a characteristic rise in serum FSH levels that occurs in the absence of a simultaneous rise in LH levels. It is not known whether this singular FSH secretion is dependent upon a differential responsiveness of the gonadotrophs to the pattern of pulsatile GnRH release or is instead driven by a GnRH-independent mechanism. We have assessed the GnRH dependence of this singular FSH secretion by testing the ability of a potent GnRH antagonist (GnRHa: WY-45760) to block FSH and testicular responses to photostimulation. Photoinhibited hamsters were transferred from a short-day (6L:18D) to a long-day photoperiod (16L:8D). Hamsters received two daily injections of a GnRH antagonist or vehicle (VEH). After 0 (short day), 3, 5, 10, 30, or 40 days the hamsters were killed; plasma was assayed for FSH, LH, and testosterone (T), and testes weights were recorded. Testes were sectioned and analyzed for tubular development. In VEH-treated animals, testicular weights increased after photostimulation, reaching mean values of 514 mg by 30 days. Treatment with GnRHa resulted in a significant (p < 0.01) attenuation of testicular growth after 30 days of photostimulation (mean testes weight = 110.1 mg). In VEH-treated hamsters there was a rapid increase in FSH levels after photostimulation that became significant by 5 days and peaked at 10 days. In the GnRHa-treated group, however, these FSH increments were completely blocked at 5 days and significantly reduced at 10 days compared to the values in the corresponding VEH-treated groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗