PubMed Health⌕ Search

Biomedical subjects

N Mrosovsky

Publications and source records attributed to N Mrosovsky.

At least 19 recordsLinked to original sources
PubMed1992

Phase response curve to anisomycin in tau mutant hamsters.

Administration of the protein synthesis inhibitor, anisomycin, to wild type hamsters produces phase shifts in their circadian rhythms that have similarities to shifts produced by non-photic behavioral stimulation. A mutation that shortens the period of rhythms in hamsters results in altered responsiveness to non-photic input. However, responses of the mutants to anisomycin are unaffected: their phase response curve (PRC) for anisomycin is similar to that of wild types. This suggests that 1) anisomycin is not acting on mechanisms specifically involved in non-photic behavioral phase shifting, and 2) the mutation affects the non-photic input pathway or the pacemaker itself at a point that is upstream from anisomycin's site of action.

Animals↗
PubMed1992

Gene expression in the geniculate induced by a nonphotic circadian phase shifting stimulus.

We examined the effect of a nonphotic stimulus (running in a novel wheel) on the induction of Fos-related proteins in the two well-established neural components of the circadian clock: the suprachiasmatic nucleus (SCN) and the intergeniculate leaflet (IGL) of the lateral geniculate complex. There was no induction of Fos immunoreactivity (IR) in the SCN, but the IGL showed distinct Fos IR in animals whose running levels were associated with maximal rhythm shifts. Induction of Fos immunoreactivity was greatest at circadian phases when wheel running induces phase shifts. This temporal and spatial specificity of Fos induction is evidence that the intergeniculate leaflet mediates nonphotic signals to the circadian clock.

Animals↗
PubMed1992

Nonphotic phase shifting in hamster clock mutants.

Golden hamsters with the tau mutation were kept in the dark and induced to become active through confinement to a novel running wheel for 3 hr. The response of the mutants to this nonphotic phase-shifting stimulus differed from that of wild-type hamsters. The mutants showed larger phase shifts, and their phase response curves differed in shape, with an advance portion at about circadian time 24, a phase at which wild types show delays. The results establish that the tau mutation, in addition to its already known effects, alters the response of the circadian system to nonphotic events.

Animals↗
PubMed1992

Behavioral inhibition of circadian responses to light.

Circadian locomotor rhythms in rodents may be synchronized by either photic or nonphotic events that produce phase shifts of the rhythm. Little is known, however, about how these two types of stimuli interact to produce entrainment. The well-characterized circadian photic response of the golden hamster was examined in situations where a short light pulse and locomotor activity, a nonphotic event, occurred simultaneously. Light-induced phase advances were attenuated when animals were active during light exposure. The results show that circadian responses to light depend upon the environmental situation in which the light is given, and call into question the implicit assumption in circadian rhythm research that phase shifting and entrainment to light-dark cycles depend simply on photic activation of well-known retinofugal pathways. Moreover, since light therapy is becoming an important component in the treatment of circadian-based disorders in humans, the results emphasize the need for evaluation of the behavioral aspects of light therapy protocols.

Animals↗
PubMed1991

Double-pulse experiments with nonphotic and photic phase-shifting stimuli.

Three-hour pulses of novelty-induced wheel running in the early to middle subjective day of golden hamsters produced phase advances of 2-3 hr. This phase shifting could be almost totally abolished by a light pulse following within 3 hr of the exercise pulse. When light pulses occurred about 8 hr after the exercise pulses, the phase-advancing effects of the latter were enhanced. Consideration of the amplitude of the phase response curve (PRC) for light pulses alone, in the test paradigms used here, showed that nonphotic and photic phase shifts did not combine additively. Antagonistic and synergistic interactions between photic and nonphotic shifts may have to be taken into account if it transpires that exercise in people can be used to assist adjustment to new schedules after crossing time zones, or in shiftwork.

Animals↗
PubMed1991

Hepatocellular carcinoma in Richardson's ground squirrels (Spermophilus richardsonii): evidence for association with hepatitis B-like virus infection.

During studies of seasonal obesity, a high frequency of hepatic neoplasms was observed in Richardson's ground squirrels. Of 12 Richardson's ground squirrels examined thoroughly, 7 had mild or moderate degrees of chronic portal hepatitis and 6 (50%) had hepatocellular carcinoma. Serological tests for hepadnavirus surface antigen, anti-core antibody and virion DNA that recognize the ground squirrel hepatitis virus of California ground squirrels (Spermophilus beecheyi) were uniformly negative. Southern blot analyses of EcoRI digests of liver cell DNA demonstrated 3.2 kb fragments that hybridized with a ground squirrel hepatitis virus-specific probe in nontumorous liver tissue from 6 of 10 ground squirrels and in hepatocellular carcinoma specimens from 2 of 5 squirrels indicating infection with a hepadnavirus related to ground squirrel hepatitis virus. Failure, however, to detect serum antibody to ground squirrel hepatitis core antigen suggested probable antigenic differences between the ground squirrel hepatitis virus of California ground squirrels and the putative Richardson's ground squirrel agent. Further studies are required to fully characterize the hepadnavirus of Richardson's ground squirrels and to determine its relationship to hepatocarcinogenesis in this species.

Animals↗
PubMed1990

Triazolam and phase-shifting acceleration re-evaluated.

In two experiments, triazolam (2.5 and 1.5 mg/animal) failed to significantly enhance the rate of reentrainment of hamsters (Mesocricetus auratus) to an 8-hr advance of their light-dark cycle. Evidently the phase-shifting effects of triazolam are not robust. The animals did not run much in their wheels in response to the drug in these two experiments. In a third experiment, triazolam (0.5 and 2.5 mg/animal) produced phase advances of activity rhythms of hamsters in the dark. In this experiment, running in response to the drug was greater. Hamsters given triazolam but confined to their nest boxes over the next few hours did not show phase shifts. The phase-shifting effects of triazolam (when they do occur) appear to be mediated through activity increases. Triazolam-treated hamsters became ataxic in all three of these experiments. Suggestions that triazolam may be useful in ameliorating rhythm disturbances in people should be treated with a caution.

Animals↗
PubMed1989

Behavioural entrainment of circadian rhythms.

This paper reviews the discovery and characterization of a behavioural system for entrainment of circadian rhythms. This behavioural system depends on non-photic inputs but interacts with the light-entrainment system. Non-photic stimuli can be powerful quantitatively: behavioural events can shift rhythms by several hours. Non-photic entrainment offers scope for rephasing biological rhythms in circumstances where light input from the environment is inadequate.

Animals↗
PubMed1989

Running activity mediates the phase-advancing effects of dark pulses on hamster circadian rhythms.

Pulses of darkness can phase-shift the circadian activity rhythms of hamsters, Mesocricetus auratus, kept in constant light. Dark pulses under these conditions alter photic input to the circadian system, but they also commonly trigger wheel-running activity. This paper investigates the contribution of running activity to the phase-shifting effects of dark pulses. A first experiment showed that running activity by itself can phase-shift rhythms in constant light. Hamsters were induced to run by being confined to a novel wheel for 3-5 h. When this was done at circadian times (CT) 0, 6, and 9, the mean steady-state phase-shifts were 0.6 h, 3.5 h, and 2.3 h, respectively. The latter two values are at least as large as those previously obtained with dark pulses of similar durations and circadian phases. A second experiment showed that restricting the activity of hamsters during 3-h dark pulses at CT 9 reduces the amplitude of the phase-shifts. Unrestrained animals phase-advanced by 1.1 h, but this shift was halved in animals whose wheel was locked, and completely abolished in animals confined to nest boxes during the dark pulse. Activity restriction in itself (without dark pulses) had only minimal phase-delaying effects on free-running rhythms when given between ca. CT 10 and CT 13. These results support the idea that, in hamsters at least, dark pulses affect the circadian system mostly by altering behavioural states rather than by altering photic input to the internal clock.

Animals↗
PubMed1989

Large phase-shifts of circadian rhythms caused by induced running in a re-entrainment paradigm: the role of pulse duration and light.

Bouts of induced wheel-running, 3 h long, accelerate the rate of re-entrainment of hamsters' activity rhythms to light-dark (LD) cycles that have been phase-advanced by 8 h (Mrosovsky and Salmon 1987). The bouts of running are given early in the first night of the new LD cycle, and by the second night the phase advance in activity onset already averages 7 h. Such large shifts contrast with the mean phase advance of less than 1 h at the peak of the phase response curve when hamsters in constant darkness (DD) experience 2-h pulses of induced activity (Reebs and Mrosovsky 1989). The present paper investigates pulse duration and light as possible causes for the discrepancy in shift amplitude between these two studies. In a first experiment, pulses of induced wheel-running 1 h, 3 h, or 5 h long were given at circadian times (CT) 6 and 22-2 to hamsters free-running in DD. Pulses given at CT 6 caused phase-advances of up to 2.8 h, whereas pulses at CT 22-2 resulted in delays of up to 1.0 h. Shifts after 3-h and 5-h pulses did not differ, but were larger than after 1-h pulses, and larger than after the 2-h pulses given in DD by Reebs and Mrosovsky (1989). Thus 3 h appears to be the minimum pulse duration necessary to obtain maximum phase-shifting effects. In a second experiment, the re-entrainment design of Mrosovsky and Salmon (1987) was repeated with the light portion of the shifted LD cycle eliminated.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Anorexic effects of interleukin 1 in the rat.

Interleukin 1 (IL-1) administration produces anorexia. Among unanswered questions about this effect are 1) whether it plays a role in the cachexia associated with chronic infection and cancer, and 2) whether IL-1 acts directly on food intake or indirectly by first lowering the set point for body weight. To investigate these questions, rats were infused with recombinant IL-1 continuously for 14 days through osmotic minipumps. Tolerance to the anorexic effects of the infusion developed within a few days. Control experiments showed that neither loss of IL-1 potency nor failure in the delivery system were responsible for recovery of food intake. Prior weight reduction completely overrode the anorexic effects of IL-1; previously food-restricted rats were hyperphagic initially despite receiving IL-1. This result is consistent with the view that IL-1 lowers the set point for body weight, but the development of tolerance prevented the full evaluation of this interpretation.

Animals↗
PubMed1989

Effects of induced wheel running on the circadian activity rhythms of Syrian hamsters: entrainment and phase response curve.

The goal of this study was to provide an example of nonsocial and nonphotic entrainment in Syrian hamsters, together with a corresponding phase response curve (PRC). Fourteen male hamsters were given 2-hr bouts of induced activity (mostly wheel running) at 23.83-hr intervals in constant darkness (DD). The activity onsets of 10 hamsters entrained to this manipulation, with no anticipatory activity present. After entrainment, the rhythms resumed free-running from a time 0.66-3.91 hr after the onset of the last bout of induced activity. Postentrainment free-running periods were shorter than pre-entrainment values. The PRC for 2-hr pulses of induced activity in DD revealed phase advances induced in some animals between circadian time (CT) 4 and CT 11 (approximately the last half of the hamsters' rest period), and delays between CT 23 and CT 3 and between CT 17 and CT 20. The CTs for phase advances are compatible with the phase angle differences observed between rhythm and zeitgeber at the end of entrainment. Many features of the results (not all animals entraining, PRC characteristics, lack of observable anticipation to the daily stimuli, phase relationship between zeitgeber and activity rhythms) are similar to those from a previous study on social entrainment in this species (Mrosovsky, 1988). These similarities reinforce the idea that induced activity and social zeitgebers act on activity rhythms via a common mechanism.

Animals↗
PubMed1989

Nonphotic enhancement of adjustment to new light-dark cycles: masking interpretation discounted.

The adjustment of hamsters to advanced light-dark (LD) cycles can be greatly accelerated by scheduling a single 3-hr bout of extra activity in a novel running wheel, starting about 7 hr before the time when the animals become active in the preceding LD cycle. The present experiments were designed to provide stronger evidence that this effect depends on a shift in the pacemaker rather than on masking. It was shown that when hamsters were put into continuous darkness (DD) 1 day after the exercise-accelerated phase shift, their free-running rhythms took off from a time nearer to the onset of darkness in the new LD cycle than in the preceding LD cycle. An incidental finding was that in DD the free-running period of the hamsters with the accelerated phase shifts was longer than that of the control animals. Further evidence that the 3-hr exercise pulse had produced a greater phase advance than that occurring in undisturbed control animals was obtained by giving a light pulse at the same clock time to all animals after they had been in DD for 8 days. The animals that had previously exercised for the additional 3-hr phase-advanced in response to the light pulse, while the undisturbed control animals phase-delayed.

Adaptation, Physiological↗
PubMed1988

Phase response curves for social entrainment.

Phase shifts in free-running activity rhythms of male golden hamsters, Mesocricetus auratus, often occur when they establish a new territory and home after a cage change. Similar shifts also often occur after pairs of animals interact with each other for half an hour. When these events take place during the middle of the hamsters' subjective day, they produce phase advances: when late in the subjective night, they produce phase delays. Repeated social interactions at the same time of day can entrain activity rhythms in a way consistent with the shape of the phase response curves. Not all individuals become entrained, as is predictable from the modest amplitude of the phase response curve. The effects of social interactions and of other disturbances may be mediated through an oscillator phased by general arousal. The present findings have implications for the interpretation of drug-induced changes in biological rhythms.

Animals↗