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F W Turek

Publications and source records attributed to F W Turek.

At least 37 records · Page 2Linked to original sources
PubMed2000

Sleep in the Wistar-Kyoto rat, a putative genetic animal model for depression.

The Wistar-Kyoto (WKY) rat exhibits several behavioral and hormonal abnormalities often associated with depression. One of the hallmarks of depression consists of alterations in the sleep-wake cycle, particularly in rapid eye movement (REM) sleep. If the WKY rat is indeed an animal model for depression, we hypothesized that it should also show sleep abnormalities relative to the control strain, the Wistar (WIS) rat Under baseline conditions, WKY rats showed a 50% increase in total REM sleep time during the 12 h light phase and an increase in sleep fragmentation during both the light and dark phase. The WKY rats also exhibited lower EEG power densities over the entire frequency range (0.2-25.0 Hz) during REM sleep. After a 6 h sleep deprivation, the REM sleep rebound was more pronounced during the dark but not the light phase in the WKY rats. Since the WKY rat represents a genetic model for depression with altered EEG sleep patterns, this strain may be particularly useful for investigating the relationship between depression and sleep abnormalities.

Animals↗
PubMed2000

Twenty-four-hour profiles of serum leptin in siberian and golden hamsters: photoperiodic and diurnal variations.

Serum leptin concentrations were obtained from male Siberian hamsters (Phodopus sungorus) and golden hamsters (a.k.a. Syrian, Mesocricetus auratus) housed on long [light:dark (LD) 16:8] and short (LD 6:18) photoperiods for 10-11 weeks. Blood samples were collected at 45-min intervals for 24 h from individual animals using an in-dwelling atrial catheter. In Siberian hamsters, exposure to short photoperiods as compared to long photoperiods reduced body weight (32.5 +/- 1.5 vs 47.7 +/- 1.1 g) and leptin (24-h mean: 5.3 +/- 0.4 ng/ml vs 18.6 +/- 2.1 ng/ml). Although photoperiod influenced the temporal distribution of leptin in golden hamsters, the main effect of photoperiod on leptin levels in golden hamsters did not reach significance (24-h mean: 7.1 +/- 1.0 ng/ml vs 5.1 +/- 0.8 ng/ml.). Body weights of golden hamsters did not vary significantly following exposure to short photoperiod for 11 weeks (178.3 +/- 3.6 g in LD 6:18 vs 177.8 +/- 7.3 g in LD 16:8). There was no nocturnal increase in serum leptin in either species. Marked interindividual differences were apparent in individual leptin profiles. Periodogram analysis revealed that only a few animals exhibited 24-h periodicities; the presence of a significant 24-h periodicity was more common in hamsters exposed to short days. Photoperiod-associated differences in the 24-hour profile of leptin secretion may be the result of photoperiod-associated changes in feeding behavior or metabolism. A full understanding of the regulation of leptin secretion in multiple time domains may enhance our understanding of the function of leptin.

Animals↗
PubMed2000

Locomotor response to an open field during C57BL/6J active and inactive phases: differences dependent on conditions of illumination.

Time of day has proven to be a source of variability in diverse behavioral measures. Knowledge of the pattern of this temporal effect as well as its origin (exogenous or endogenous) is essential for a precise description of any behavior. This study analyzed the effect of the external light-dark cycle and the internal rest-activity rhythm on the response of C57BL/6J mice to a novel environment. In a first experiment, animals maintained in a 12:12-h light-dark cycle were tested in an open field at six different times of day. A diurnal rhythm of ambulation in the open field was observed with greater levels of activity exhibited by those groups tested at night. Long-term and short-term behavioral habituation to spatial novelty were also affected by phase of the light-dark cycle. A second experiment was designed to control for any direct effect of the light-dark cycle by keeping the animals in dim green light where entrainment was maintained by a skeleton photoperiod (two 15-min bright-light pulses separated by 12 hours of green, dim light). This second group of animals was tested at two different circadian phases under the same conditions of illumination. One group was tested during the subjective night and another group during the subjective day, i.e., 2 or 14 h after the onset of the active phase, as assessed by wheel-running behavior. No effect of circadian phase on ambulation or habituation of this response to the open field was observed in these animals. Taken together, these results suggest that spatial novelty is equally arousing regardless of circadian phase and that the conditions of illumination can dramatically alter the response to a novel environment.

Animals↗
PubMed2000

Metabolic influences on circadian rhythmicity in Siberian and Syrian hamsters exposed to long photoperiods.

Calorie restriction and other situations of reduced glucose availability in rodents alter the entraining effects of light on the circadian pacemaker located in the suprachiasmatic nuclei. Siberian and Syrian hamsters are photoperiodic species that are sexually active when exposed to long summer-like photoperiods, while both species show opposite changes in body mass when transferred from long to short or short to long days. Because metabolic cues may fine tune the photoperiodic responses via the suprachiasmatic nuclei, we tested whether timed calorie restriction can alter the photic synchronization of the light-entrainable pacemaker in these two hamster species exposed to long photoperiods. Siberian and Syrian hamsters were exposed to 16 h:8 h light:dark cycles and received daily hypocaloric (75% of daily food intake) or normocaloric diet (100% of daily food intake) 4 h after light onset. Four weeks later, hamsters were transferred to constant darkness and fed ad libitum. The onset of the nocturnal pattern of locomotor activity was phase advanced by 1.5 h in calorie-restricted Siberian hamsters, but not in Syrian hamsters. The lack of phase change in calorie-restricted Syrian hamsters was also observed in individuals exposed to 14 h:10 h dim light:dark cycles and fed with lower hypocaloric food (i.e. 60% of daily food intake) 2 h after light onset. Moreover, in hamsters housed in constant darkness and fed ad lib., light-induced phase shifts of the locomotor activity in Siberian hamsters, but not in Syrian hamsters were significantly reduced when glucose utilization was blocked by pretreatment with 500 mg/kg i.p. 2-deoxy-D-glucose. Taken together, these results show that the photic synchronization of the light-entrainable pacemaker can be modulated by metabolic cues in Siberian hamsters, but not in Syrian hamsters maintained on long days.

Animals↗
PubMed2000

Differential regulation of pituitary gonadotropin subunit messenger ribonucleic acid levels in photostimulated Siberian hamsters.

FSH levels begin to rise 3-5 days after male Siberian hamsters are transferred from inhibitory short photoperiods to stimulatory long photoperiods. In contrast, LH levels do not increase for several weeks. This differential pattern of FSH and LH secretion represents one of the most profound in vivo examples of differential regulation of the gonadotropins. The present study was undertaken to characterize the molecular mechanisms controlling differential FSH and LH synthesis and secretion in photostimulated Siberian hamsters. First, we cloned species-specific cDNAs for the three gonadotropin subunits: the common alpha subunit and the unique FSHbeta and LHbeta subunits. All three subunits share high nucleotide and predicted amino acid sequence identity with the orthologous cDNAs from rats. We then used these new molecular probes to examine the gonadotropin subunit mRNA levels from pituitaries of short-day male hamsters transferred to long days for 2, 5, 7, 10, 15, or 20 days. Short-day (SD) and long-day (LD) controls remained in short and long days, respectively, from the time of weaning. We measured serum FSH and LH levels by RIA. FSHbeta, LHbeta, and alpha subunit mRNA levels were measured from individual pituitaries using a microlysate ribonuclease protection assay. Serum FSH and pituitary FSHbeta mRNA levels changed similarly following long-day transfer. Both were significantly elevated after five long days (2.3- and 3.6-fold, respectively; P < 0.02) and declined thereafter, but they remained above SD control values through 20 long days. Alpha subunit mRNA levels also increased significantly relative to SD control values (maximum 2-fold increase after seven long days; P < 0.03), although to a lesser extent than FSHbeta. Neither serum LH nor pituitary LHbeta mRNA levels changed significantly following long-day transfer. The results indicate that long-day-associated increases in serum FSH levels in Siberian hamsters reflect an underlying increase in pituitary FSHbeta and alpha subunit mRNA accumulation.

Animals↗
PubMed2000

Daytime naps in darkness phase shift the human circadian rhythms of melatonin and thyrotropin secretion.

To systematically determine the effects of daytime exposure to sleep in darkness on human circadian phase, four groups of subjects participated in 4-day studies involving either no nap (control), a morning nap (0900-1500), an afternoon nap (1400-2000), or an evening nap (1900-0100) in darkness. Except during the scheduled sleep/dark periods, subjects remained awake under constant conditions, i.e., constant dim light exposure (36 lx), recumbence, and caloric intake. Blood samples were collected at 20-min intervals for 64 h to determine the onsets of nocturnal melatonin and thyrotropin secretion as markers of circadian phase before and after stimulus exposure. Sleep was polygraphically recorded. Exposure to sleep and darkness in the morning resulted in phase delays, whereas exposure in the evening resulted in phase advances relative to controls. Afternoon naps did not change circadian phase. These findings indicate that human circadian phase is dependent on the timing of darkness and/or sleep exposure and that strategies to treat circadian misalignment should consider not only the timing and intensity of light, but also the timing of darkness and/or sleep.

Adult↗
PubMed1999

High corticosterone levels in prenatally stressed rats predict persistent paradoxical sleep alterations.

Prenatal stress predisposes rats to long-lasting disturbances that persist throughout adulthood (e.g., high anxiety, dysfunction of the hypothalamo-pituitary-adrenal axis, and abnormal circadian timing). These disturbances parallel to a large extent those found in depressed patients, in which hypercortisolemia and sleep alterations may be related to stress-inducing events. We studied sleep-wake parameters in control and prenatally stressed adult rats (3-4 months old) and examined possible relationships with their corticosterone levels (determined at 2 months of age). Under baseline conditions, prenatally stressed rats showed increased amounts of paradoxical sleep, positively correlated to plasma corticosterone levels. Other changes include increased sleep fragmentation, total light slow-wave sleep time, and a slight decrease in the percentage of deep slow-wave sleep relative to total sleep time. During recovery sleep from acute restraint stress, all sleep changes persisted and were correlated with stress-induced corticosterone secretion. High corticosterone levels under baseline conditions as well as an acute stress challenge may thus predict long-term sleep-wake alterations in rats. Taken together with other behavioral and hormonal abnormalities in prenatally stressed animals, the pronounced changes in sleep-wake parameters that are similar to those found in depressed patients suggest that prenatal stress may be a useful animal model of depression.

Analysis of Variance↗
PubMed1999

Gold-thioglucose-induced hypothalamic lesions inhibit metabolic modulation of light-induced circadian phase shifts in mice.

The circadian clock located in the suprachiasmatic nuclei is entrained by the 24-h variation in light intensity. The clock's responses to light can, however, be reduced when glucose availability is decreased. We tested the hypothesis that the ventromedial hypothalamus, a key area in the integration of metabolic and hormonal signals, mediates the metabolic modulation of circadian responses to light by injecting C57BL/6J mice with gold-thioglucose (0.6 g/kg) which damages glucose-receptive neurons, primarily located in the ventromedial hypothalamus. Light pulses applied during the mid-subjective night induce phase delays in the circadian rhythm of locomotor activity in mice kept in constant darkness. As previously observed, light-induced phase delays were significantly attenuated in fed mice pre-treated with 500 mg/kg i.p. 2-deoxy-D-glucose and in hypoglycemic mice fasted for 30 h, pre-treated with 5 IU/kg s.c. insulin or saline, compared to control mice fed ad libitum. In contrast, similar metabolic challenges in mice with gold-thioglucose-induced hypothalamic lesions did not significantly affect light-induced phase delays compared to mice treated with gold-thioglucose and fed ad libitum. These results indicate that destruction of gold-thioglucose-sensitive neurons in the ventromedial hypothalamus prevent metabolic regulation of circadian responses to light during shortage of glucose availability. Therefore, the ventromedial hypothalamus may be a central site coordinating the metabolic modulation of light-induced phase shifts of the circadian clock.

Animals↗
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

Chronobiotic effects of gepirone, a potential antidepressant with 5HT1A receptor partial agonist properties.

Abnormal timing in the circadian system is reported in endogenous depression. Gepirone, a 5HT1A receptor partial agonist, has anxiolytic and antidepressant properties. We determined whether gepirone was able to modify the functioning of the circadian system. Single i.p. injections of gepirone in hamsters induced phase-advances in the circadian activity rhythm when administered during the subjective day, but had no effect when given during the subjective night. Single i.p. gepirone injections also blocked the phase-shifting effects of a light pulse, at a time when gepirone by itself had no effect on the activity rhythm. Chronic gepirone treatment in hamsters kept under a 14/10 light-dark cycle induced a phase-advance in the activity rhythm, modifying the phase-relationship between this rhythm and the light-dark cycle. After transfer to constant darkness, gepirone-treated hamsters showed a shortened free-running period of activity, compared to controls. Both acute and chronic gepirone treatment thus have major effects on the circadian rhythm of locomotor activity in rodents. In view of the hypothesized role for disturbed circadian rhythms in the pathophysiology of depression, and the use of 5HT-related drugs for its treatment, the results provide further support for the possibility that some of the therapeutic effects of these compounds may be due to their effects on temporal organization.

Animals↗
PubMed1999

Altered circadian responses to light in streptozotocin-induced diabetic mice.

Diabetes mellitus affects the daily expression of many behavioral and metabolic processes. Recent studies indicate that changes in brain glucose metabolism alter the entraining effects of light of the circadian pacemaker. To test whether diabetes-associated diurnal changes are related to alterations in the responses of the circadian pacemaker to light, photic phase resetting of the circadian rhythm of locomotor activity was analyzed in diabetic mice housed in constant darkness. Multiple low doses of streptozotocin, which damages pancreatic beta-insulin-producing cells, were used to render C57BL/6J mice mildly diabetic. In those mice treated with streptozotocin, serum glucose was increased by 25% and circadian responses to light either were increased by 40% for phase delays or were close to those observed in control animals for phase advances. Furthermore, insulin-induced hypoglycemia normalized light-induced phase delays in diabetic animals, without altering those in nondiabetic mice. These results show that abnormalities of daily temporal organization associated with diabetes can result from altered circadian responses to the daily variation in ambient light. Such alterations could be normalized with appropriate insulin therapy.

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↗
PubMed1999

Reduced glucose availability attenuates circadian responses to light in mice.

To test whether circadian responses to light are modulated by decreased glucose availability, we analyzed photic phase resetting of the circadian rhythm of locomotor activity in mice exposed to four metabolic challenges: 1) blockade of glucose utilization induced by 2-deoxy-D-glucose (2-DG), 2) fasting (food was removed for 30 h), 3) insulin administration, and 4) insulin treatment after fasting. In mice housed in constant darkness, light pulses applied during early subjective night induced phase delays of the rhythm of locomotor activity, whereas light pulses applied during late subjective night caused phase advances. There was an overall reduction of light-induced phase shifts, with a more pronounced effect for delays, in mice pretreated with 500 mg/kg ip 2-DG compared with mice injected with saline. Administration of glucose with 2-DG prevented the reduction of light-induced phase delays. Furthermore, phase delays were reduced in fed mice pretreated with 5 IU/kg sc insulin and in fasted mice injected with saline or insulin compared with control fed mice. These results show that circadian responses to light are reduced when brain glucose availability is decreased, suggesting a metabolic modulation of light-induced phase shifts.

Animals↗
PubMed1999

The search for circadian clock and sleep genes.

In recent years, there has been extraordinary progress in elucidating the molecular components of the mammalian circadian clock system. The discovery of circadian clock genes in lower organisms (such as fruit flies and fungi), which show many similarities with clock genes in mammals, together with advances in mouse molecular genetics have led to major new discoveries on the molecular and genetic basis of mammalian circadian rhythms. This article reviews both of these lines of research from an historical perspective and discusses how these lines have merged to provide unique insights into the molecular mechanisms of circadian function. The review also speculates on how the discovery of circadian clock genes may lead directly or indirectly to the discovery of mammalian sleep genes. The determination of the molecular mechanisms via which circadian clock genes (and their protein products) regulate the timing and the need for sleep, and the identification of new genes involved in sleep regulation, may produce new information on the genetic and molecular control of sleep which could ultimately lead to the development of new treatments for sleep disorders.

Animals↗
PubMed1999

Androgen receptor, estrogen receptor alpha, and estrogen receptor beta show distinct patterns of expression in forebrain song control nuclei of European starlings.

In songbirds, singing behavior is controlled by a discrete network of interconnected brain nuclei known collectively as the song control system. Both the development of this system and the expression of singing behavior in adulthood are strongly influenced by sex steroid hormones. Although both androgenic and estrogenic steroids have effects, androgen receptors (AR) are more abundantly and widely expressed in song nuclei than are estrogen receptors (ER alpha). The recent cloning of a second form of the estrogen receptor in mammals, ER beta, raises the possibility that a second receptor subtype is present in songbirds and that estrogenic effects in the song system may be mediated via ER beta. We therefore cloned the ER beta complementary DNA (cDNA) from a European starling preoptic area-hypothalamic cDNA library and used in situ hybridization histochemistry to examine its expression in forebrain song nuclei, relative to the expression of AR and ER alpha messenger RNA (mRNA), in the adjacent brain sections. The starling ER beta cDNA has an open reading frame of 1662-bp, predicted to encode a protein of 554 amino acids. This protein shares greater than 70% sequence identity with ER beta in other species. We report that starling ER beta is expressed in a variety of tissues, including brain, pituitary, skeletal muscle, liver, adrenal, kidney, intestine, and ovary. Similar to reports in other songbird species, we detected AR mRNA-containing cells in several song control nuclei, including the high vocal center (HVc), the medial and lateral portions of the magnocellular nucleus of the anterior neostriatum, and the robust nucleus of the archistriatum. We detected ER alpha expression in the medial portion of HVc (also called paraHVc) and along the medial border of the caudal neostriatum. ER beta was not expressed in HVc, in the medial and lateral portions of the magnocellular nucleus of the anterior neostriatum, in the robust nucleus of the archistriatum, or in area X. In contrast, ER beta mRNA-containing cells were detected in the caudomedial neostriatum and medial preoptic area in a pattern reminiscent of P450 aromatase expression in the same brain regions in other songbirds. These data suggest that estrogenic effects on the song system are not mediated via ER beta-producing cells within song nuclei. Nonetheless, the overlapping expression of ER beta- and aromatase-producing cells in the caudomedial neostriatum suggests that locally synthesized estrogens may act via ER beta, in addition to ER alpha, to mediate seasonal or developmental effects on nearby song nuclei (e.g. HVc).

Amino Acid Sequence↗
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↗