The dorsomedial hypothalamic nucleus is not necessary for the expression of circadian food-anticipatory activity in rats

Restricted daytime feeding generates food-anticipatory activity (FAA) by entrainment of a circadian pacemaker separate from the light-entrainable pacemaker located in the SCN. The dorsomedial hypothalamic nucleus (DMH) has been proposed as the site of food-entrainable oscillators critical for the expression of FAA, but another study found no effects of complete DMH ablation on FAA. To account for these different results, the authors examined methodological factors, including (1) cage configuration and feeding method and (2) use of social cues. Intact and DMH-ablated rats were maintained on one 4-h daily meal in the middle of the light period, using caging and feeding methods matching those of Gooley et al. (2006). Rats with partial or complete DMH ablation were less nocturnal during ad lib food access but exhibited normal FAA during restricted feeding, as quantified by FAA magnitude, ratios, latency to appearance, duration, and precision. To evaluate the use of social cues, intact rats naive to restricted-feeding schedules were food deprived for 72 h on 4 tests. Daytime activity increased during food deprivation, but the magnitude and waveform of this activity was not influenced by the presence of food-entrained rats exhibiting robust FAA in adjacent cages. Thus, hungry intact rats do not use social cues to anticipate a daily mealtime, suggesting that DMH-ablated rats do not anticipate meals by reacting to sounds from food-entrained intact rats in adjacent cabinets. These results confirm our previous finding that the DMH is not critical for normal expression of FAA in rats, and this observation is extended to food restriction methodologies used by other labs. The methodological differences that do underlie discrepant results remain unresolved, as does the location of food-entrainable oscillators, input pathways, and output pathways critical for FAA.     

Evidence for time-of-day dependent effect of neurotoxic dorsomedial hypothalamic lesions on food anticipatory circadian rhythms in rats

The dorsomedial hypothalamus (DMH) is a site of circadian clock gene and immediate early gene expression inducible by daytime restricted feeding schedules that entrain food anticipatory circadian rhythms in rats and mice. The role of the DMH in the expression of anticipatory rhythms has been evaluated using different lesion methods. Partial lesions created with the neurotoxin ibotenic acid (IBO) have been reported to attenuate food anticipatory rhythms, while complete lesions made with radiofrequency current leave anticipatory rhythms largely intact. We tested a hypothesis that the DMH and fibers of passage spared by IBO lesions play a time-of-day dependent role in the expression of food anticipatory rhythms. Rats received intra-DMH microinjections of IBO and activity and body temperature (T(b)) rhythms were recorded by telemetry during ad-lib food access, total food deprivation and scheduled feeding, with food provided for 4-h/day for 20 days in the middle of the light period and then for 20 days late in the dark period. During ad-lib food access, rats with DMH lesions exhibited a lower amplitude and mean level of light-dark entrained activity and T(b) rhythms. During the daytime feeding schedule, all rats exhibited food anticipatory activity and T(b) rhythms that persisted during 2 days without food in constant dark. In some rats with partial or total DMH ablation, the magnitude of the anticipatory rhythm was weak relative to most intact rats. When mealtime was shifted to the late night, the magnitude of the food anticipatory activity rhythms in these cases was restored to levels characteristic of intact rats. These results confirm that rats can anticipate scheduled daytime or nighttime meals without the DMH. Improved anticipation at night suggests a modulatory role for the DMH in the expression of food anticipatory activity rhythms during the daily light period, when nocturnal rodents normally sleep.     

Effects of early weaning on the circadian rhythm and behavioral satiety sequence in rats

The objective of this work was to study the effect of early weaning on circadian rhythm and the behavioral satiety sequence in adult rats. Male Wistar rat pups were weaned for separation from the mother at 15 (D15), 21 (D21) and 30 (D30) days old. Body weight and food intake was measured every 30 days until pups were 150 days old. At 90 days of age, the circadian rhythm of food intake was evaluated every 4 h for three days. Behavioral satiety was evaluated at 35 and 100 days of age. This work demonstrated that body weight and food intake were not altered, but the behavioral satiety sequence demonstrated that the D15 group delayed satiety compared with the D30 group at 100 days of age. In the circadian rhythm of the food intake study, early weaning (D15) changed food intake in the intermediary period of the light phase and in the intermediary period of the dark phase. In conclusion, our study showed that early weaning may alter the feeding behavior mainly in relation to satiety and the circadian rhythm of feeding. It is possible that the presence of other environmental stimuli during early weaning can cause hyperphagia and deregulate the mechanisms of homeostasis and body weight control. This study supports theories that depict insults during early life as determinants of chronic diseases.     

The circadian rhythm of a behavioral photoresponse in the dinoflagellate Gyrodinium dorsum

Summary The circadian rhythm of the photoresponse to blue light in the dinoflagellate Gyrodinium dorsum Kofoid was investigated by the use of a closed circuit television system. The initial cessation of movement upon stimulation (stop-response) was used as the index of light reception. Under constant dark conditions cells grown on a 12L:12D regime show an endogenous circadian rhythm in their stop-response with maximum responsiveness occurring approximately one hour before the beginning of the expected light phase. This rhythmic response was only observed if the cells were irradiated with red light (620 nm) prior to stimulation with blue light. After preirradiation both far-red reversibility and the shift in the stop-response action spectrum from 470 nm to 490 nm could also be demonstrated. These findings may be related to the diurnal migration of marine dinoflagellates.This study was supported by National Science Foundation grant GB 5137.     

Glucagon-like peptide-1 of brainstem origin activates dorsomedial hypothalamic neurons in satiated rats

A high number of neurons express c-fos in response to unlimited food intake in fasted rats in the ventral subdivision of the hypothalamic dorsomedial nucleus (DMHv). We report here, that in same conditions, limited food consumption failed to induce Fos expression in DMHv neurons suggesting that satiation should be one of the important signals that activate these neurons. The possible origin of fibers conducting satiation signals to the DMHv could be in the lower brainstem, especially glucagon-like peptide-1 (GLP-1)-containing neurons in the nucleus of the solitary tract (NTS). We demonstrate that GLP-1-immunoreactive fibers and fiber terminals topographically overlap with activated Fos-positive neurons in the DMHv in refed rats. Using immunocytochemistry and in situ hybridization histochemistry, we demonstrated GLP-1 receptors in Fos-expressing neurons of the DMH. Unilateral transections of ascending GLP-1-containing fibers from the NTS inside the pons in refed rats (unlimited food consumption) resulted in a dramatic decrease in the density of GLP-1 fibers and in the number of Fos-immunoreactive neurons in the DMHv, but only on the side of the transection. Contralateral to the transection, neither the GLP-1 fiber density nor the number of Fos-positive cells changed significantly. Meanwhile, the density of GLP-1 immunoreactivity was markedly accumulated in transected nerve fibers caudal to the cuts, as a consequence of the interruption of the ascending GLP-1 transport route. These findings suggest that the solitary-hypothalamic projections may represent the neuronal route through GLP-1 neurons of the NTS activate DMHv neurons via GLP-1 receptors by conveying information on satiety.     

Relationships between behavioral rhythms, plasma corticosterone and hypothalamic circadian rhythms

Circadian rhythms in physiological processes and behaviors were compared with hypothalamic circadian rhythms in norepinephrine (NE) metabolites, adrenergic transmitter receptors, cAMP, cGMP and suprachiasmatic nucleus (SCN) arginine vasopressin (AVP) in a single population of rats under D:D conditions. Eating, drinking and locomotor activity were high during the subjective night (the time when lights were out in L:D) and low during the subjective day (the time when lights were on in L:D). Plasma corticosterone concentration rose at subjective dusk and remained high until subjective dawn. Binding to hypothalamic alpha 1- and beta-adrenergic receptors also peaked during the subjective night. Cyclic cGMP concentration was elevated throughout the 24-hr period except for a trough at dusk, whereas DHPG concentration peaked at dawn. Arginine vasopressin levels in the suprachiasmatic nucleus peaked in the middle of the day. No rhythm was found either in binding to the alpha 2-adrenergic receptor, or in MHPG or cAMP concentration. Behavioral and corticosterone rhythms, therefore, are parallel to rhythms in hypothalamic alpha 1- and beta-receptor binding and NE-release. Cyclic GMP falls only at dusk, suggesting the possibility that cGMP inhibits activity much of the day and that at dusk the inhibition of nocturnal activity is removed. SCN AVP, on the other hand, peaking at 1400 hr, may play a role in the pacemaking function of the SCN that drives these other rhythms.     

Persistence of the circadian rhythm of dehydroepiandrosterone in the brain, but not in the plasma, of castrated and adrenalectomized rats

In adrenalectomized and orchidectomized rats, the removal of the steroidogenic endocrine glands is associated with a near-disappearance of corticosterone (B) from plasma and brain; circadian variations of B and of plasma dehydroepiandrosterone (D), characteristic of the intact rat, are no more detected. By contrast, analyses of brain D measurements by the cosinor method demonstrate a persisting circadian rhythm of large amplitude.     

Loss of circadian rhythm of blood pressure following acute stroke

Background  

Epidemiology of acute stroke in developing countries differs from that in the developed world, for example, the age at stroke, risk factors, subtypes of stroke and prognosis. Hypertension remains a dominant risk factor and prognostic indicator in patients with stroke in all communities. The risk of stroke is directly related to elevations of blood pressure. A number of clinical studies have shown that the control of hypertension leads to a reduction in the incidence of stroke in a community. However there is still considerable controversy surrounds the changes in blood pressure in various subtypes of strokes and problem of management of elevated BP after stroke. We studied the circadian rhythm of blood pressure in patients following acute stroke.     

The Paramecium circadian behavioral rhythm: light phase response curves and entrainment

The population of a ciliate protozoan, Paramecium multimicronucleatum, exhibits a circadian rhythm as measured by the number of the cells traversing an observation point ("traverse frequency," or TF). The present study examined phase shifting of the TF rhythm by administering 2-hr light pulses at different phases of the circadian cycle to cultures free-running in constant darkness (DD). The results were summarized in a phase response curve (PRC), categorized as Type 1. This PRC indicated a relatively narrow phase zone insensitive to the light pulse ("dead zone"). Entrainment of the rhythm to light pulses repeated at 24-hr intervals was also examined, and it was found that the rhythm gradually reached a steady state, following several transient cycles, with the pulses falling at a phase corresponding to the narrow dead zone. Such a steady-state rhythm, with a minimum at approximately 3 hr after the pulse and a maximum at approximately 12 hr after the pulse, was mathematically simulated by superimposing a response function to the pulse on a sinusoidal function representative of the free-running rhythm in DD.     

Role of dorsomedial hypothalamic neuropeptide Y in energy homeostasis

Hypothalamic neuropeptide Y (NPY) is primarily expressed in the arcuate nucleus (Arc) and the dorsomedial hypothalamus (DMH). Although Arc NPY gene expression is responsive to circulating leptin, the regulation of DMH NPY expression is leptin-independent. DMH NPY expression is increased in response to chronic food restriction, but not acute food deprivation. DMH NPY expression is elevated in pair-fed OLETF rats lacking cholecystokinin (CCK)-1 receptors. A role for CCK in controlling DMH NPY expression is demonstrated by the down-regulation of DMH NPY by parenchymal DMH CCK administration in intact rats. Moreover, access to running wheels normalizes body weight and prevents altered DMH NPY expression of OLETF rats. Together, these data suggest that DMH NPY plays an important role in feeding and body weight control.     

Postnatal development of the circadian rhythm of circulating blood cells in rats

In the present study the variations in the leukocyte and erythrocyte counts were investigated in the peripheral blood within the light and darkness periods during the postnatal development of rats. The animals were kept under an artificial illumination regime (12 hours light, 12 hours darkness), and examined at the ages of 7, 14, 21, 28, 35 and 45 days, and in maturity (56 days). Erythrocyte counts exhibited no light-dark rhythm. The circadian rhythm of leukocyte counts developed in male and female laboratory rats in the fourth week of age.     

Suppression of feeding by cholecystokinin but not bombesin is attenuated in dorsomedial hypothalamic nuclei lesioned rats

Rats with dorsomedial hypothalamic lesions (DMN-L) or sham operations were injected IP with saline or the satiety peptide cholecystokinin (CCK) at 3.0 and 6.0 micrograms/kg at the onset of the dark phase. Food consumption was then measured 15, 30 and 60 min later. Compared to saline baseline intake, CCK suppressed feeding during the first 30 min following injection in the sham operated group but not in the DMN-L group. Bombesin (BBS), another satiety peptide was also injected (4.0 and 8.0 micrograms/kg) into the two groups. BBS produced significant and comparable suppression of feeding in both DMN-L and sham operated rats. In a third trial a large dose of CCK (12.0 micrograms/kg) was injected into the two groups as described above. The CCK suppressed feeding for 60 min in the control group. CCK also attenuated feeding in the DMN-L group, but for only 30 min. However, even this suppression was reduced compared to the control group. The data suggest that the DMN may play a role in CCK induced satiety.