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Biomedical subjects

M Menaker

Publications and source records attributed to M Menaker.

At least 91 records · Page 5Linked to original sources
PubMed1986

Melatonin-induced increases in serotonin concentrations in specific regions of the chicken brain.

Day-night differences in the concentrations of melatonin and serotonin (5HT) were measured in several regions of the chicken brain, pineal gland and serum. Melatonin concentrations are higher at midnight than at midday in 8 of the 10 tissues studied although the amplitudes of these rhythms varied greatly. Day-night differences in the pineal, hypothalamus, thalamus, retina and pons-midbrain regions had the highest amplitudes. 5HT concentrations were rhythmic in only 3 of the tissues studied: the hypothalamus, thalamus and retina. These were also the areas of highest 5HT concentration. Exogenous melatonin, injected at midday, was taken up with similar patterns; the pineal, hypothalamus, thalamus and pons-midbrain contained more melatonin 20 min after injection than did other tissues. The rate of decline of melatonin concentration varied little among all tissues studied, suggesting that the differences among tissue concentrations were due to selective uptake mechanisms rather than specialized degradation pathways. The effects of exogenous melatonin on 5HT concentration were restricted to hypothalamus, thalamus, pons-midbrain, retina and pineal. No effect was seen in cerebellum, optic tectum, neostriatum, hippocampus and medulla oblongata. Together, these data strongly suggest that pineal (and exogenous) melatonin is selectively taken up primarily by three brain regions, hypothalamus, thalamus and pons-midbrain, in which it produces increases in 5HT concentrations. Regional selectivity of uptake may be the mechanism by means of which the effects of melatonin on 5HT-mediated function are restricted to specific brain areas.

Animals↗
PubMed1985

Bicuculline blocks circadian phase delays but not advances.

Phase delays of hamster locomotor rhythms, which normally can be produced by light pulses given in the early subjective night, were blocked by bicuculline, a selective antagonist of gamma-aminobutyric acid (GABA) activity. Phase advances induced by light pulses given in the late subjective night were unaffected by bicuculline. This suggests that GABA may be involved in the mediation of some, but not all, light input to the mammalian circadian system. Furthermore, it raises the possibility that light input may be mediated at different circadian time points by functionally separate pathways.

Animals↗
PubMed1985

Eyes--the second (and third) pineal glands?

The pineal gland, the retinas and perhaps other tissues as well may in some species produce melatonin that appears in significant quantities in the circulation. In at least one species, Japanese quail, the circadian rhythm in the levels of circulating melatonin reflects contributions from both the pineal and the retinas; in other species circulating melatonin may come exclusively from the pineal or perhaps only from the eyes. Comparative behavioural and physiological data from several bird and lizard species indicate that retinas and pineal glands fulfil similar endocrine roles. Current evidence suggests that in iguanid lizards either retinas or pineal glands, but not both in the same species, have important regulatory influences on circadian organization. This suggests that it should be relatively easy to influence the melatonin-forming ability of a tissue by natural selection, an interpretation bolstered by our finding that the ability to synthesize melatonin has been inadvertently eliminated in the pineal glands of laboratory mice, presumably by the selection involved in producing inbred strains. The genetics of melatonin synthesis in mice is briefly discussed.

Animals↗
PubMed1984

Is the avian circadian system a neuroendocrine loop?

Avian circadian organization is a result of a complex interaction of photoreceptive and oscillatory components. The known components include the pineal gland, the lateral eyes, the suprachiasmatic nuclei (SCN), and extraocular brain photoreceptors. The pathways by which these components integrate circadian rhythmicity suggest a neuroendocrine loop in which the SCN inhibits pineal and ocular oscillators during the course of subjective day via a multisynaptic neuronal pathway which includes the superior cervical ganglia (SCG). During the night, the pineal in turn inhibits SCN activity via its secretion of the hormone melatonin into the blood circulation. This neuroendocrine loop, it is proposed, synchronizes multiple oscillators within each component and maintains the stability and precision of the system.

Animals↗
PubMed1983

Daily rhythms of serotonin metabolism in the medial hypothalamus of the chicken: effects of pinealectomy and exogenous melatonin.

Indoleamine levels in punches of the medial hypothalamus containing the suprachiasmatic nuclei (SCN) of 4-week-old cockerels were determined by HPLC-EC. Melatonin levels in punches were determined by radioimmunoassay (RIA). Daily rhythms of serotonin (5-HT) and of its metabolite 5-hydroxy-3-indoleacetic acid (5-HIAA) were observed; levels were higher at midnight than at midday. A daily rhythm with the same phase in punch melatonin content was also observed. Pinealectomy at 1 week after hatching abolished the 5-HIAA and melatonin rhythm in 4-week-old birds but did not abolish the 5-HT rhythm. Injections of melatonin (0.5 mg/kg) increased 5-HT, 5-HIAA and melatonin levels in the hypothalamic punches. These results indicate that circulating melatonin of pineal origin may act to increase 5-HT turnover and/or release in the SCN. They suggest a link between the circadian secretion of pineal melatonin and the regulation of 5-HT projections to the hypothalamus from the raphe nuclei in the brainstem of the chicken. We have previously shown that the rhythmic secretion of melatonin by the pineal is influenced by oscillators in the brain via the superior cervical ganglia. The results reported here indicate that melatonin in turn may regulate brain oscillators, suggesting a neuroendocrine loop within the avian circadian system.

Animals↗
PubMed1983

Sympathetic regulation of chicken pineal rhythms.

Adult hens were chronically cannulated and held in light-dark (LD) 12:12 h lighting regimes or in constant darknesS (DD). Periodic blood sampling for 5-9 days revealed circadian rhythms in plasma melatonin titres. Superior cervical ganglionectomy (SCG-X) performed 1 week after hatching had little or no effect on these rhythms in LD, but unlike normals. SCG-X birds did not sustain persistent rhythms in DD. In SCG-X birds, norepinephrine (NE) infusion for 12 h of each 24 h in DD significantly reduced plasma melatonin titres during the infusion and re-established a rhythm. After each experiment, hens were killed, their pineals were removed and assayed by HPLC-EC for NE, dopamine (DA), serotonin (5-HT) and 5-hydroxy-3-indole-acetic acid (5-HIAA). SCG-X resulted in a 90% depletion of pineal NE: DA content was reduced to undetectable levels. Pineal 5-HT and 5-HIAA were also reduced by SCG-X. The chicken pineal contains circadian oscillators which persist in vitro8.19.29. The results reported here suggest that noradrenergic fibres from the SCG regulate the pineal's inherent rhythmicity. NE normally released from sympathetic terminals during the bird's day may synchronize oscillators within the pineal by inhibiting melatonin synthesis.

Animals↗
PubMed1983

Light-induced decrease of serotonin N-acetyltransferase activity and melatonin in the chicken pineal gland and retina.

In the pineal gland and retina of chickens, light exposure at night when serotonin N-acetyltransferase (NAT) activity levels are high causes a 4--5-fold decrease in NAT activity. The t1/2 of NAT inactivation is 10 min and the kinetics of inactivation are similar in the pineal gland and retina. A brief pulse of light can initiate the process of NAT inactivation which continues in the dark for 30 min before a partial recovery of NAT activity occurs. In blinded chicks, there is less inactivation of pineal NAT by light than in intact chicks, indicating that the eyes are involved in the pineal's response to light. In chicks that have had their superior cervical ganglia removed inactivation of pineal NAT by light is intermediate between that of intact and blind chicks, indicating that ganglionectomy does not completely mimic the effects of blinding. The pineal gland itself is light-sensitive in culture. Light causes a 4--5-fold decrease in NAT activity in static organ culture, and inhibits melatonin release in flow-through organ culture. Drugs that increase cyclic nucleotide levels in cells (cholera toxin, RO 20-1724, monobutyryl cyclic AMP, monobutyryl cyclic GMP) block the NAT decrease by light, whereas high potassium or EGTA do not block this light-induced NAT inactivation.

Acetyltransferases↗
PubMed1983

Temperature-compensated circadian clock in the pineal of Anolis.

The pineal organ of the lizard Anolis carolinensis can be maintained for up to 10 days in superfused organ culture. During this time it synthesizes and releases melatonin into the medium flowing slowly over it. Collection of timed aliquots of medium and subsequent analysis for melatonin by radioimmunoassay reveal circadian rhythms of melatonin output by the isolated pineal. These rhythms persist for many cycles in constant darkness and at several constant ambient temperatures ranging from 22 to 37 degrees C. The period of the rhythm is temperature compensated (Q10 approximately equal to 1.14) and the rhythm is synchronized by light-dark cycles imposed on the cultured gland. This isolated vertebrate organ displays the three major properties of circadian systems and must therefore contain one or more circadian oscillators.

Animals↗
PubMed1983

Sex differences in the circadian control of hamster wheel-running activity.

The circadian pacemaker that underlies the wheel-running activity of hamsters was studied in males and females. Sex differences were found in the mechanism by which the pacemaker entrains to light-dark cycles and in the timing of activity onset. When exposed to a light-dark cycle with a period of 24.75 h (with 1 h of light/cycle), males show a greater ability to maintain entrainment than do females. This difference in the upper limit of entrainment appears due to a sex difference in the magnitude of light-induced phase shifts. A small difference in free-running period may also contribute to the sex difference in entrainment. Two weeks after castration of adults, the sex difference in entrainment is not affected, indicating that the difference does not depend on circulating gonadal steroids or on estrous cyclicity of the female. However, castration of females at an early age increases their ability to entrain, whereas long-term castration of males seems to reduce entrainment ability. During entrainment to a 24-h light-dark cycle (LD 14:10), females were found to begin their daily activity before males and before castrated females. This difference is consistent with a sex difference in the magnitude of light-induced phase shifts and in entrainment of the pacemaker. However, evidence is given that the sex difference in activity onset might also be caused by a sex difference in the relationship of locomotor activity to the pacemaker in intact males and females.

Animals↗
PubMed1982

Role of the suprachiasmatic nuclei in the circadian system of the house sparrow, Passer domesticus.

The suprachiasmatic nuclei (SCN) of the hypothalamus are necessary for the persistence of free running circadian activity rhythms in house sparrows. Suprachiasmatic lesions abolish circadian locomotor rhythms in constant darkness. The locomotor activity of lesioned sparrows was analyzed with two different power spectral analysis methods and was found to be arrhythmic. There was a weak correlation between the extent of damage to the SCN and the relative amplitude of the power spectral density in the circadian frequency range. In light-dark cycles (LD 12:12), the locomotor behavior of lesioned sparrows was rhythmic and similar to that of intact birds. However, entrainment was disrupted in SCN-lesioned sparrows exposed to a short photoperiod light cycle (LD 1:24). These results demonstrate that the SCN are crucial for the generation of overt circadian rhythmicity in birds. The fact that SCN lesions abolish circadian rhythms in sparrows and several mammalian species suggests that vertebrate circadian organization may be based on differentially weighted interactions among the pineal, the SCN, and perhaps other brain regions.

Animals↗
PubMed1981

Pineal and retinal serotonin N-acetyltransferase activity: modulation by phosphate.

Serotonin N-acetyltransferase (NAT) activity in chicken pineal homogenates is increased 16-fold in the presence of high-molarity phosphate buffer (0.35 M) as compared with its activity in low-molarity (0.05 M) phosphate buffer. This phosphate effect on NAT does not depend on ionic, osmotic, or pH changes; rather, it appears to be a direct effect of phosphate on NAT activity. Phosphate also stabilizes NAT activity to thermal inactivation and inactivation caused by incubation at 4 degrees C for 48 h. Stimulation of NAT activity by phosphate occurs only in chick pineal and retina, not in chick cerebrum, cerebellum or liver, nor in rat pineal or other tissues tested. There is a correlation between the occurrence of the phosphate effect and the occurrence of endogenous NAT circadian rhythmicity and light inactivation. The effect of phosphate on NAT activity in homogenates may reflect physiological mechanisms of NAT regulation.

Acetyltransferases↗
PubMed1980

Circadian rhythms of melatonin release from individual superfused chicken pineal glands in vitro.

The pineal gland of birds contains one or more circadian oscillators that play a major role in overall temporal organization. We have developed a flow-through culture system for the isolated pineal by which we can measure the release of melatonin continuously from superfused glands over long periods of time. Chicken pineals release melatonin rhythmically, and these rhythms persist in vitro with a circadian oscillation. In light cycles the release of melatonin is strongly rhythmic; however, in constant conditions the amplitude of the rhythm is lower and appears to be damping. Light has at least two effects upon the isolated pineal: cyclic light input synchronizes the rhythm, and acute light exposure at night rapidly inhibits melatonin release. The cultured avian pineal clearly offers great potential as a model system for the study of vertebrate circadian oscillators and may open the way for an analysis of mechanism.

Animals↗
PubMed1980

Retinal rhythms in chicks: circadian variation in melantonin and serotonin N-acetyltransferase activity.

There is a large-amplitude circadian rhythm of indoleamine metabolism in the retina-pigment epithelium of the chicken. N-Acetyltransferase activity (arylamine acetyltransferase; acetyl-CoA:arylamine N-acetyltransferase, EC 2.3.1.5) and melatonin content are 15-fold higher at night than during the day in a cycle of a 4-fold increase during the subjective night. Light at midnight inactivates N-acetyltransferase and lowers melatonin. N-Acetyltransferase activity is found predominantly in the retina. The circadian rhythm of this enzyme activity persists in pinealectomized chicks. Thus the pineal is not responsible for retinal indoleamine rhythms. Retinal and pineal levels of N-acetyltransferase activity behave similarly under several conditions. In the chicken, the eye is a major site of rhythmic indoleamine metabolic activity.

Acetyltransferases↗
PubMed1980

Hamsters through time's window: temporal structure of hamster locomotor rhythmicity.

The temporal patterns of running-wheel locomotor activity of a group of 15 golden hamsters (Mesocricetus auratus) are described in detail. The temporal patterns of activity and the behavior of activity bouts in these animals provide the basis for a hypothetical multioscillator framework underlying locomotor activity. The framework consists of a pacemaker that controls the transitions between two continuous states, activity time and rest time, each composing approximately half of the circadian cycle. Activity time appears as a "window" during which the expression of locomotor bouts controlled by additional circadian oscillators is permitted. In our model, whether or not locomotor activity is expressed as well as its detailed temporal pattern are functions of the phase relationships between the window pacemaker and bout oscillators.

Animals↗
PubMed1980

Interaction of estradiol and progesterone: effects on circadian locomotor rhythm of female golden hamsters.

The phase and activity level of the locomotor rhythms of female golden hamsters (Mesocricetus auratus) vary in synchrony with the 4-day estrous cycle. We investigated the effects of estradiol and progesterone administration in ovariectomized hamsters to explore the interaction of these two ovarian hormones in modulating circadian locomotor rhythms. Silastic implants of estradiol shorten the period length of the rhythm, change the pattern and level of activity, and decrease the observed variance of the activity onset. Progesterone implants have no effects on the rhythm when given alone; however, when progesterone is given in combination with estradiol, all three estradiol-induced changes are blocked. These results correlate well with the observed locomotor behavior of normal female hamsters. If the levels of both estradiol and progesterone in the serum are taken into account, this correlation holds for a number of hormonal conditions including those found during the 4-day estrous cycle as well as during pregnancy and lactation. These data suggest that progesterone antagonizes the effects of estradiol in the normal animal and that the interaction of estradiol and progesterone modulates the circadian activity of female hamsters on a day-to-day basis.

Animals↗
PubMed1979

The pineal gland: a pacemaker within the circadian system of the house sparrow.

Transplantation of pineal tissue into the anterior chamber of the eye rapidly reestablishes rhythmicity in arhythmic pinealectomized sparrows and also transfers the phase of the donor bird's rhythm to the host. Thus, the transplanted pineal does not merely permit rhythmicity to be expressed but rather transfers an oscillation that controls the remainder of the circadian system and restores the capacity for self-sustained rhythmicity. Long-term recordings, during which sparrosw were exposed to various lighting conditions, demonstrate a remarkable similarity between the circadian system in normal birds and that in birds bearing pineal transplants.

Animals↗