Browsing by Author "Wollnik, Franziska"

Now showing 1 - 20 of 24

Open Access
Blood pressure in rats : a comparison of a multifactorial experimental design to measurements in an outbred stock
(1984) Büttner, Dietmar; Hackbarth, Hansjoachim; Wollnik, Franziska; Borggreve, H.
Systolic blood pressure was measured in males of 8 inbred strains and 1 outbred stock of rats 5 times over a period of 20 min on 5 consecutive days. The strain means ranged between 107·9 mmHg and 149·3 mmHg. The estimated variance between strains (V = 248·7 mmHg) was about 5 times higher than the variance within strains (V = 54·3 mmHg). The intraindividual variance within strains was relatively constant (V = 24·0-37·6 mmHg), while the interindividual variance varied to a great extent (V = 4·5-44·5 mmHg) from strain to strain. The outbred stock showed values of blood pressure and components of variance similar to those of a single inbred strain. Thus, by investigation of a battery of 8 inbred strains in a multifactorial experimental design a greater phenotypic variability due to genetic strain differences is achieved than by measurements in a single outbred stock.
Open Access
Effect of lithium carbonate on activity level and circadian period in different strains of rats
(1994) Hafen, Thomas; Wollnik, Franziska
Lithium, an important pharmacological agent for the treatment of manic-depressive illness in humans, is known to lengthen the circadian period in a number of different species. Recent experiments, on the other hand, suggest that pharmacological agents may affect the circadian system indirectly through an increase or decrease of activity. To explore the interaction between pharmacological and activity effects on the circadian system, lithium was administered chronically to three different strains of rats (ACI, BH, and LEW) while wheel-running activity was studied quantitatively. Two of these inbred strains (BH and LEW) show profound abnormalities in their circadian activity rhythms, namely, a reduced overall level of activity and bimodal or multimodal activity patterns. Wheel-running activity was monitored for 4 weeks under baseline conditions, followed by 3 weeks with lithium treatment (0.3% Li2CO3 administered with food) and 4 weeks with normal food. Treatment with lithium (average intake per day = 3.6 ± 0.2 mg) consistently decreased both the overall level and the circadian amplitute of the activity rhythm. The free-running period τ was slightly lengthened during lithium treatment, while the most dramatic effect on period was observed after lithium withdrawal. Correlation analysis, however, revealed only a small negative correlation between activity level and period length, which proved significantly only for animals of the ACI strain. Our data support the traditional interpretation that lithium lengthens circadian period by a direct pharmacological effect on the circadian pacemaker rather than through indirect effects of activity feedback.
Open Access
Effect of photoperiod on the development of wheel-running activity rhythms in LEW/Ztm rats
(1993) Siebert, Ursula; Wollnik, Franziska
Wheel-running activity of LEW/Ztm rats is characterized by a multimodal pattern consisting of two activity bouts about 3-5 h apart. In this study we investigated the development of activity rhythms in LEW rats born and raised under three different photoperiods (LD 18:6, LD 12:12, and LD 6:18). Wheel-running activity was measured for 6 weeks in LD and for another 6 weeks in constant darkness (DD). The length of the photoperiod influenced the phase relationship between the two activity bouts only during the first week after weaning. Then, the characteristic activity pattern was established independently of the length of the photoperiod. However, development under long photoperiods (LD 18:6) resulted in a temporary increase in the level of activity and a significant shortening of the free-running period under DD. These results indicate that the multimodal activity pattern displayed by LEW rats is controlled by separate activity oscillators that establish their unique phase relationship early during development.
Open Access
Effects of adult or perinatal hormonal environment on ultradian rhythms in locomotor activity of laboratory LEW/Ztm rats
(1986) Wollnik, Franziska; Döhler, Klaus-Dieter
Four experiments were performed with male and female rats of the inbred strain LEW/Ztm maintained under a light-dark schedule of 12:12 hours. The animals were subject to castration (GOX) or ovariectomy (OVX), estradiol 17β-implantation (E2-capsules), and perinatal hormonal treatments with testosterone propionate (TP) and an androgen antagonist (acetate, CA). Results indicated a difference in the locomotor activity pattern between the two sexes as a result of the endogenous estradiol levels of the adult animals. The activity pattern of male LEW rats was characterized by ultradian rhythms of 4 and 4.8 hr periods. The female LEW rats, on the other hand, generally exhibited a clear circadian activity pattern and no ultradian activity rhythms. Following ovariectomy, each of the females showed distinct ultradian rhythms. These disappeared after E2-implantation. Castration of adult males had no effect on the ultradian activity pattern. Implantation of E2-capsules resulted in a marked decrease of the ultradian activity components. Perinatal treatment of the males with an androgen antagonist (CA) did not appear to effect ultradian rhythms during adulthood. Females treated perinatally with testosterone showed a significant increase in the ultradian activity components. This effect is assumed to be due to low estrogen levels in these animals during adulthood. Our study supports the assumption that ultradian rhythms are a result of changes in the phase relationships between several circadian oscillators. The synchrony of these oscillations seems to be facilitated by estradiol.
Open Access
Effects of chronic administration and withdrawal of antidepressant agents on circadian activity rhythms in rats
(1992) Wollnik, Franziska
Experimental and clinical studies indicate that clinical depression may be associated with disturbances of circadian rhythms. To explore the interaction between circadian rhythmicity, behavioral state, and monoaminergic systems, the present study investigated the effects of chronic administration and withdrawal of the following antidepressant agents on circadian wheel-running rhythms of laboratory rats: a) moclobemide, a reversible and selective monoamine oxidase (MAO) type A inhibitor; b) Ro 19-6327, a selective MAO type B inhibitor; c) desipramine, a preferential norepinephrine reuptake inhibitor; d) clomipramine and e) fluoxetine, both serotonin reuptake inhibitors; and f) levoprotiline, an atypical antidepressant whose biochemical mechanism is still unknown. Wheel-running activity rhythms were studied in three inbred strains of laboratory rats (ACI, BH, LEW) under constant darkness (DD). Two of these inbred strains (BH and LEW) show profound abnormalities in their circadian activity rhythms, namely, a reduced overall level of activity and bimodal or multimodal activity patters. Chronic treatment with moclobemide and desipramine consistently increased the overall level, as well as the circadian amplitude, of the activity rhythm. Furthermore, the abnormal activity pattern of the LEW strain was changed into a unimodal activity pattern like that of other laboratory rats. The free-running period τ was slightly shortened by moclobemide and dramatically shortened by desipramine. Effects of moclobemide and desipramine treatment on overall activity level and duration were reversed shortly after termination of treatment, whereas long aftereffects were observed for the free-running period. All other substances tested had no systematic effects on the activity rhythms of any of the strains. The fact that moclobemide and desipramine altered the period, amplitude, and pattern of circadian activity rhythms is consistent with the hypothesis that monoaminergic transmitters play a significant role in the neuronal control of behavioral state and circadian rhythmicity. Although the present study found that some antidepressives affect parameters of circadian rhythmicity, it could not demonstrate a common effect of all classes of antidepressives.
Open Access
Effects of complete and partial SCN lesions on ultradian and circadian locomotor activity rhythms in LEW/Ztm rats : [abstract]
(1987) Wollnik, Franziska; Turek, Fred W.
Both circadian end ultradian rhythms in locomotor activity have been observed in laboratory rats. However, while the neural pacemaker involved in the regulation of the circadian activity rhythm (as well as many other rodent circadian rhythms) appears to be located in the suprachiasmatic nuclei (SCN), the neural basis for the generation of behavioral ultradian rhythms remains unclear, Complete and partial lesions of the SCN were used to determine if the same neural substitute may underlie both circadian and ultradian rhythms in the wheel-running activity of LEW/Ztm rats.
Open Access
Effects of constant darkness and constant light on circadian organization and reproductive responses in the ram
(1988) Ebling, Francis J. P.; Lincoln, Gerald A.; Wollnik, Franziska; Anderson, Norah
The relationship between circadian rhythms in the blood plasma concentrations of melatonin and rhythms in locomotor activity was studied in adult male sheep (Soay rams) exposed to 16-week periods of short days (8 hr of light and 16 hr of darkness; LD 8:16) or long days (LD 16:8) followed by 16-week periods of constant darkness (dim red light; DD) or constant light (LL). Under both LD 8:16 and LD 16:8, there was a clearly defined 24-hr rhythm in plasma concentrations of melatonin, with high levels throughout the dark phase. Periodogram analysis revealed a 24-hr rhythm in locomotor activity under LD 8:16 and LD 16:8. The main bouts of activity occurred during the light phase. A change from LD 8:16 to LD 16:8 resulted in a decrease in the duration of elevated melatonin secretion (melatonin peak) and an increase in the duration of activity corresponding to the changes in the ratio of light to darkness. In all rams, a significant circadian rhythm of activity persisted over the first 2 weeks following transfer from an entraining photoperiod to DD, with a mean period of 23.77 hr. However, the activity rhythms subsequently became disorganized, as did the 24-hr melatonin rhythms. The introduction of a 1-hr light pulse every 24 hr (LD 1:23) for 2 weeks after 8 weeks under DD reinduced a rhythm in both melatonin secretion and activity: the end of the 1-hr light period acted as the dusk signal, producing a normal temporal association of the two rhythms. Under LL, the 24-hr melatonin rhythms were disrupted, though several rams still showed periods of elevated melatonin secretion. Significant activity rhythms were either absent or a weak component occurred with a period of 24 hr. The introduction of a 1-hr dark period every 24 hr for 2 weeks after 8 weeks under LL (LD 23:1) failed to induce or entrain rhythms in either of the parameters. The occurrence of 24-hr activity rhythm in some rams under LL may indicate nonphotoperiodic entrainment signals in our experimental facility. Reproductive re sponses to the changes in photoperiod were also monitored. After pretreatment with LD 8:16, the rams were sexually active; exposure to LD 16:8, DD, or LL resulted in a decline in all measures of reproductive function. The decline was slower under DD than LD 16:8 or LL. Conversely, after pretreatment with LD 16:8, the rams were sexually regressed, and exposure to LD 8:16, DD, or LL resulted in redevelopment of the reproductive axis; the rate of development was similar in all three treatments. The overall results illustrate that in the Soay ram the circadian organization of melatonin and activity rhythms is disrupted during pro longed exposure to DD and LL. Reproductive regression or recrudescence occurs under these constant conditions, apparently dictated by the immediate photoperiodic history.
Open Access
Estrous correlated modulations of circadian and ultradian wheel-running activity rhythms in LEW/Ztm rats
(1988) Wollnik, Franziska; Turek, Fred W.
Estrogen treatment alters the expression of ultradian activity rhythms in male and female LEW/Ztm rats. This finding raises the possibility that the expression of ultradian rhythms may vary on different days of the estrous cycle. To test this hypothesis, we recorded the circadian and ultradian wheel-running activity rhythms of entrained (LD 12:12) and free-running sexually mature LEW/Ztm females during their 4- or 5-day estrous cycle. The mean daily activity, the duration of activity, the circadian period of activity, and the occurrence of ultradian rhythms differed significantly among the days of the estrous cycle. In LD 12:12, the phase angle difference between the beginning of activity and light offset varied reliably in 5-day cycling animals. The highest daily mean of activity, the longest duration, and the shortest circadian period length were observed on the day of estrus in both entrained and free-running animals. The day of estrus was characterized by a constant high level of activity throughout the activity phase, while the days following ovulation showed a bi- or trimodal activity pattern. Power spectrum analysis revealed significant ultradian components for the days of metestrus and diestrus, but only circadian components for the days of proestrus and estrus. These results were interpreted as indicating that endogenous changes in circulating hormone levels can induce changes in the ultradian and circadian patterns of wheel-running activity in LEW/Ztm rats.
Open Access
Genetic analysis of circadian and ultradian locomotor activity rhythms in laboratory rats
(1987) Wollnik, Franziska; Gärtner, Klaus; Büttner, Dietmar
Obvious differences exist in the daily activity patterns of the LEW/Ztm and ACI/Ztm inbred strains of laboratory rats. The inbred strain ACI/Ztm shows a clear 24-h rhythm of locomotor activity. The activity pattern of the LEW/Ztm strain, however, is characterized by ultradian rhythms of 4- and 4.8-h periods. Genetic analysis of crosses between the two strains was used to examine the relative amounts of additive genetic and dominance effects for traits associated with circadian and ultradian rhythms of locomotor activity. The measured variables of the timing mechanism (amplitude c; acrophase φ; 24, 4.8-, and 4-h spectral estimates) exhibited substantial heritability, with general dominant-recessive modes of inheritance and the associated dominance variance.
Open Access
Inhibitor of protein synthesis phase shifts a circadian pacemaker in mammalian SCN
(1988) Inouye, Shin-Ichi T.; Takahashi, Joseph S.; Wollnik, Franziska; Turek, Fred W.
The suprachiasmatic nucleus (SCN) of the hypothalamus contains a circadian pacemaker that regulates many circadian rhythms in mammals. Experimental work in microorganisms and invertebrates suggests that protein synthesis is required for the function of the circadian oscillator, and recent experiments in golden hamsters suggest an acute inhibition of protein synthesis can induce phase shifts in a mammalian circadian pacemaker. To determine whether protein synthesis in the SCN region is involved in the generation of circadian rhythms in mammals, a protein synthesis inhibitor, anisomycin, was microinjected into the SCN region, and the effect on the circadian rhythm of locomotor activity of hamsters was measured. A single injection of anisomycin into the SCN region induced phase shifts in the circadian activity rhythm that varied systematically as a function of the phase of injection within the circadian cycle. These results suggest that protein synthesis may be involved in the generation of circadian rhythms in mammals and that the anatomic site of action of anisomycin is within the hypothalamic suprachiasmatic region.
Open Access
Intraventricular application of c-Fos und Jun B antisense-oligonucleotides blocks light-induced phase shifts of the mammalian circadian system : [abstract]
(1994) Wollnik, Franziska; Gillardon, Frank; Bravo, Rodrigo; Zimmermann, Manfred; Brysch, Wolfgang; Schlingensiepen, Karl-Hermann; Herdegen, Thomas
-
Open Access
Neonatal sex reversal of the brain and the urinary excretion of sex dependent proteins (SDP) in the rat
(1987) Alt, Jeannette; Jarzab, Barbara; Wollnik, Franziska; Döhler, Klaus-Dieter
In contrast to females adult male rats excrete a variety of low molecular weight sex dependent urinary proteins (SDP). Electrophoretic separation of these proteins yields at least 8 protein bands which are arranged in typical patterns. The present study was performed to investigate the effert of sexual differentiation, which can be influenced by neonatal hormone treatment, on production and excretion of the individual SDP-bands (I - VIII). Two major groups of rats were studied: one group was neonatally treated with testosterone propionate (TP, females) or cyproterone acetate (males). Another group of rats with or without neonatal TP-treatment were gonadectomized in adulthood and subsequently implanted with TP. The results demonstrated that SDP excretion is mainly related to the circulating plasma testosterone levels. The sexual differentiation of the brain, however, influences the quantity of SDP excreted which is especially evident for bands I and II. Neonatal cyproterone had influence on these two bands only. The results demonstrate that the hormonal mechanisms regulating tho excretion of SDP varies in respect to the different protein bands. The functional role of sexual brain differentiation on the excretion of SDP and the detailed mechanisms by which the brain may control this extcretion remain to be determined.
Open Access
Phase shifting the circadian clock with cycloheximide : response of hamsters with an intact or a split rhythm of locomotor activity
(1989) Wollnik, Franziska; Turek, Fred W.; Majewski, Philip; Takahashi, Joseph S.
Systematic administration of the protein synthesis inhibitor, cycloheximide, induced both phase advances and phase delays in the circadian rhythm of wheel-running activity in hamsters (Mesocricetus auratus) maintained in constant darkness or constant light. The magnitude and direction of the phase shifts were dependent on the circadian time (CT) of drug treatment. The phase response curves in constant darkness and constant light were of similar general shape, but they differed in the overall mean amplitude of the phase shifts. Maximal phase advances were observed after injections around CT 6-8, maximal delays at CT 0-2. Injections of various doses of cycloheximide at CT 0 induced a dose-dependent phase delay in the rhythm with a maximum delay induced by 10 mg cycloheximide. Injections of cycloheximide in animals with a split activity rhythm caused phase shifts of both components in the same direction (20/39) and in different directions (10/39). The results support the hypothesis that 80S ribosomal protein synthesis plays an important role in the biochemical mechanisms of circadian systems.
Open Access
Physiology and regulation of biological rhythms in laboratory animals : an overview
(1989) Wollnik, Franziska
Biological rhythms have been observed in practically all groups of laboratory mammals and at every level of physiological and behavioural organization. Biological rhythms are classified according to their period as ultradian (<24 h), circadian (~24 h), infradian(>24 h), and seasonal or circannual rhythms (~1 year). This review outlines what is known about the neurobiology of biological rhythms in mammals and describes the hierarchical order in which ultradian, circadian and infradian rhythms are related to each other. The article does not attempt to catalogue every physiological variable showing rhythmical fluctuations in laboratory mammals. Rather, it focuses on the basic concepts of circadian rhythms and recent advances made in our understanding of the physiology of the internal clock controlling circadian and other biological rhythms.
Open Access
The protective reflex of Bowerbankia (Bryozoa) : calibration and use to indicate movements of the medium beneath a capillary surface wave
(1980) Wiese, Konrad; Wollnik, Franziska; Jebram, Diethardt
The protective polypide-withdrawal reflex ofBowerbankia imbricata (Bryozoa, Ctenostomata) was released by controlled oscillations of the medium (water). The range of effective oscillation frequencies extends from 10 to 200 Hz. The displacements at the threshold of the reflex are 120 μm (peak to peak) at 10 Hz, an average of 30 μm in the range 40-80 Hz, and 150 μm at 200 Hz. The thresholds of oscillation velocity remain within the limits of 0.5 to 1.0 cm/s throughout the frequency range 10-110 Hz, which suggests that this parameter is involved in stimulus reception. The "all-or-none reflex movement" of the animal was employed as an indicator of the position of a defined amount of displacement of the medium beneath a capillary surface wave; this result was compared with calculated values.
Open Access
The role of Jun transcription factor expression and phosphorylation in neuronal differentiation, neuronal cell death, and plastic adaptations in vivo
(1994) Schlingensiepen, Karl-Hermann; Wollnik, Franziska; Kunst, Mechthild; Schlingensiepen, Reimar; Herdegen, Thomas; Brysch, Thomas
1. To investigate the role of the Jun transcription factors in neuronal differentiation, programmed neuronal cell death, and neuronal plasticity, we used phosphorothioate oligodeoxynucleotides (S-ODN) to inhibit selectively the expression of c-Jun, JunB, and JunD. 2. We have shown previously that in contrast to c-Jun, the JunB and JunD transcription factors are negative regulators of cell growth in various cell lines. Here we confirm this finding in primary human fibroblasts. 3. c-Jun and JunB are counterplayers not only with respect to proliferation, but also in cell differentiation. Since JunB expression is essential for neuronal differentiation, we analyzed possible posttranslational modifications of JunB after induction of PC-12 cell differentiation by nerve growth factor (NGF). 4. JunB was strongly phosphorylated after induction of PC-12 cell differentiation with NGF but not after stimulation of cell proliferation with serum. Thus, while cell proliferation is associated with c-Jun phosphorylation, cell differentiation is correlated with JunB phosphorylation. This supports the finding that c-Jun and JunB play antagonistic roles in both proliferation and differentiation. 5. The JunB transcription factor together with the c-Fos transcription factor is also inducedin vivo in the suprachiasmatic nucleus (SCN) of rat brain after a light stimulus that induces resetting of the circadian clock. 6. Using antisense oligonucleotides injected into the third ventricle, we selectively cosuppressed the two transcription factorsin vivo as shown by immunohistochemistry. Expression of c-Jun, JunD, and FosB was not affected. Inhibition of JunB and c-Fos expression prevented the light-induced phase shift of the circadian rhythm. In contrast, rats injected with a randomized control oligonucleotide showed the same phase shift as untreated animals. 7. In primary rat hippocampal cultures, anti-c-jun S-ODN selectively inhibited neuronal cell death and promoted neuronal survival. This indicates a causal role of c-Jun in programmed neuronal cell death. 8. These findings demonstrate the essential role of inducible transcription factors in the reprogramming of cells to a different functional state. Jun transcription factors play an essential role not only in fundamental processes such as cell proliferation, differentiation, and programmed neuronal cell death, but also in such complex processes as plastic adaptations in the mature brain. The inhibition of neuronal cell death by anti-c-jun S-ODN shows the great therapeutic potential of selective antisense oligonucleotides.
Open Access
SCN lesions abolish ultradian and circadian components of activity rhythms in LEW/Ztm rats
(1989) Wollnik, Franziska; Turek, Fred W.
A trimodal locomotor activity pattern has been observed in LEW/Ztm rats. Complete and partial lesions of the suprachiasmatic nucleus (SCN) were used to determine whether the same neural substrate may underlie the circadian rhythms and the ultradian modulation of wheel-running activity in these rats. Whereas sham lesions had little or no effect on the wheel-running activity pattern, complete SCN lesions resulted in a complete loss of circadian and ultradian activity components under free-running or 12:12 h light-dark cycle (12:12 LD) conditions. Ultradian and circadian activity components were still present after partial SCN lesions. Periodogram analysis for any given animal revealed that the ultradian periods were always submultiples of the entrained or free-running circadian period. Furthermore there was a high correlation between the amplitudes of circadian and ultradian spectral estimates, but with a different slope in males and females. These results indicate that in LEW/Ztm rats the SCN contributes to the control of both the circadian wheel-running rhythm and the trimodal ultradian modulation of that behavior.
Open Access
Seasonal change in the temporal organization of wheel-running activity of the European hamster, Cricetus cricetus
(1991) Wollnik, Franziska; Breit, Alexandra; Reinke, Dagmar
In this paper we demonstrate that a dramatic annual change in the temporal organization of locomotor activity goes hand in hand with the seasonal cycle of reproduction. Activity levels increased when the animals entered reproductive conditions, which occurs naturally in spring and early summer. During the 2-3 months of reproduction, a well-defined activity rhythm was observed. During the rest of the year, the level of activity was dramatically reduced and almost no rhythmic organization was detected. The question arising from these observations is whether the loss of temporal organization reflects a weakening or arrhythmia of the underlying pacemaker or whether it is due to an uncoupling of the overt activity rhythm from the central clock.
Open Access
Sex differences in the daily pattern of locomotor activity in laboratory rats
(1985) Wollnik, Franziska
The present study supplies information supporting an obvious sex difference in the daily pattern of locomotor activity in laboratory rats. Ultradian rhythms, which have been found to be genetically fixed in two inbred strains of rats, are also sex-specific. They were observed in male animals of these strains. The females failed to show any ultradian rhythmicity.
Open Access
Spontaneous short-term fluctuations in the daily pattern of heart rate, body temperature and locomotor activity in the laboratory rat
(1982) Büttner, Dietmar; Wollnik, Franziska
Heart rate (HR), body temperature (BT) and locomotor activity (LA) were measured continuously over 5 days in freely moving rats. In addition to the well-known circadian rhythms, all variables exhibited considerable fluctuations in amplitude mainly during the dark, but also in the light periods. The values of HR varied from 286 ± 12 to 470 ± 26 b.p.m. and BT from 36·15 ± 0·15°C to 38·45 ± 0·25°C. The large variability of HR, BT and LA within a single day was due more to large short-term fluctuations within periods of about 3-5 hours duration, than to differences between the light and the dark period. Good consistency of daily patterns and similarity of the 3 variables was found within the animals. Usually there were 3 or 4 regular peaks during the dark and often another peak 3-4 hours after the onset of light. Correlation coefficients, calculated on the basis of 5-min mean values, were highly significant (P<0·001) for LA vs HR (0·61-0·73), LA vs BT (0·40-0·53), and HR vs BT (0·61-0·68). Between-hour correlations were higher than these common correlations of 5-min values. HR vs BT (0·76-0·83) and LA vs BT (0·63-0·79) correlated as well as LA vs HR (0·72-0·83). The short-term fluctuations (within-hours) gave lower correlation coefficients for LA vs BT (0·23-0·32) and HR vs BT (0·29-0·41) than LA vs HR (0·40-0·70). This seems to result from a physiological delay of BT relative to HR and LA.