Biomedical subjects

M Menaker

Publications and source records attributed to M Menaker.

130 records · Page 8Linked to original sources

PubMedDate not supplied

Spectral sensitivity of a novel photoreceptive system mediating entrainment of mammalian circadian rhythms.

Environmental light cycles are the dominant synchronizers of circadian rhythms in the field, and artificial light cycles and pulses are the major tools used in the laboratory to analyse properties of circadian systems. It is therefore surprising that few studies have analysed the physical parameters of light stimuli that affect circadian rhythms. There have previously been no spectral sensitivity measurements for phase shifting the circadian rhythms of mammals and only two preliminary reports on the wavelength dependence of this response exist. Using the magnitude of phase shift caused by a single 15-min pulse of monochromatic light given 6 h after activity onset, we have now characterized the spectral sensitivity of the photoreceptors responsible for phase shifting the locomotor rhythm of the hamster (Mesocricetus auratus). The sensitivity curve for this response has a maximum near 500 nm and is similar to the absorption spectrum for rhodopsin. Although the spectral sensitivity is consistent with a rhodopsin-based photopigment, two features of the photoreceptive system that mediates entrainment are unusual: the threshold of the response is high, especially for a predominantly rod retina like that of the hamster, and the reciprocal relationship between intensity and duration holds for extremely long durations (up to 45 min). These results suggest that the photoreceptive system mediating entrainment is markedly different from that involved in visual image formation.

Animals↗

PubMedDate not supplied

Ontogeny of the pineal response to norepinephrine.

The Syrian hamster pineal displays age-dependent changes in melatonin output measured in vitro. Between the ages of 4 and 19 days, pineal melatonin generation in response to 10 microM norepinephrine (NE) increased 34-fold. Production of melatonin by cultured pineals from 1-week-old hamsters showed a clear dose responsiveness to NE: The most effective dose was 10 microM and the response declined at both higher and lower doses. When cultured pineals from 7-day-old animals were exposed to four cycles of NE in the medium (10 hr 10 microM NE: 14 hr 0 M NE), the melatonin output followed the driving rhythm with a rising lag time of 8 hr and a falling lag of 4 hr. This time course is consistent with the conclusion [Santana et al., 1990; Gonzalez-Brito et al., 1990] that transcription events lead to a long lag time between the stimulus and the onset of melatonin synthesis. In the absence of exogenous NE, melatonin output from most glands dropped to undetectable levels in just over 2 days; however, even after 3 days without NE, glands could be stimulated to produce melatonin when NE was added to the medium. When incubated with 10 microM NE for 6 hr in static culture, glands from 11- versus 4-day-old neonates produced 20 times more melatonin and had over three times higher NAT specific activity. After a 15 min incubation with 10 microM NE, cAMP content was three-fold higher in 11-compared to 4-day-old pineals. Our results demonstrate that although the pineal's response to NE increases with age, its response time is invariant throughout postnatal development.

Animals↗

PubMedDate not supplied

Factors determining the restoration of circadian behavior by hypothalamic transplants.

The expression of locomotor activity by golden hamsters is temporally controlled by circadian oscillators contained within the suprachiasmatic nucleus (SCN). A genetic mutation has been found that alters the freerunning period of the locomotor activity rhythm from the wild-type value of approximately 24 hours to approximately 20 hours in homozygous mutants. It has been shown previously that a transplant of fetal hypothalamic tissue containing the SCN to a host rendered arrhythmic by a complete lesion of the SCN restores rhythmicity with the freerunning period which is normally expressed by the donor genotype. To investigate the mechanisms by which the SCN controls the temporal organization of behavior, we made partial lesions to the SCN of hosts of one genotype, and then placed hypothalamic implants from fetal donors of a different genotype into the lesion site. By varying the size of the host's partial SCN lesion and the duration of time between lesioning and transplantation, we have attempted to alter the relative amount of host and donor control over the expression of locomotor activity. We found that the expression of donor rhythmicity requires the presence of a lesion to the host SCN, and that the incidence of donor expression increased as a function of host SCN lesion size. Neither the duration of time between lesioning and transplantation, nor the location of the transplant within the third ventricle had independent effects on the incidence of donor rhythm expression; however, there was a strong suggestion of an effect of their interaction.

Animals↗

PubMedDate not supplied

Effect of transplanting suprachiasmatic nuclei from donors of different ages into completely SCN lesioned hamsters.

The suprachiasmatic nucleus (SCN) is the primary circadian pacemaker in mammals. Ralph and colleagues /14/ provided recent new evidence for this by transplanting SCNs between golden hamsters with different genetically determined periods and producing circadian rhythms of running wheel activity with periods characteristic of the donor. We have extended these studies in order to evaluate the age range of donor tissue that can be used for transplantation. SCN of hamsters from embryonic day 11 through postnatal day 12 can serve as functional grafts to restore rhythmicity to arrhythmic SCN lesioned animals. The time between SCN transplantation and onset of rhythmicity does not depend on the age of the donor. The presence of patches containing vasoactive intestinal peptide (VIP) immunoreactive cells is a good indicator of graft success, while its absence is correlated with a lack of transplant effect. The 18 day span during which SCN tissue can be harvested for transplantation should expand the uses to which this technique can be put. Our results also suggest that it would be advantageous to examine the age range of neural tissue that can be used in other transplantation models.

Aging↗