Photoperiodic control of the seasonal variations in the daily pattern of melatonin synthesis in the European hamster, Cricetus cricetus.
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Animals↗
Biomedical subjects
A Malan
Publications and source records attributed to A Malan.
Daily variations in pineal melatonin concentrations in inbred and outbred mice.
Melatonin was measured using a specific radioimmunoassay in 1 strain of outbred mice (OF1 Swiss) and 4 strains of inbred mice, 2 of them being known to synthesize melatonin (CBA and C3H) and the 2 others being controversial (BALB/c and C57BL/6). In this study, the 5 mouse strains were able to synthesize melatonin, but the basal levels as well as the diurnal variations were very different from one strain to another. CBA and C3H strains showed a clear-cut day-night rhythm of pineal melatonin concentration, with peak levels of 276 +/- 22 pg/pineal in CBA and 135 +/- 12 pg/pineal in C3H. In BALB/c, the authors confirmed the presence of a very short melatonin peak (15 min) in the middle of the dark period. In C57BL/6 and OF1 Swiss, a very small but significant peak was observed in the middle of the darkness. In the former, another small peak was also observed at light onset. Whether these very small peaks, which may be related to the deficience of N-acetyl transferase activity reported by others, have a physiological meaning remains to be determined.
Animals↗
Fos-like immunoreactivity in the circadian timing system of calorie-restricted rats fed at dawn: daily rhythms and light pulse-induced changes.
Daily rhythms of pineal melatonin, body temperature, and locomotor activity are synchronized to the light-dark cycle (LD) via a circadian clock located in the suprachiasmatic nuclei (SCN). A timed caloric restriction in rats fed at dawn induces phase-advances and further phase-stabilization of these rhythms, suggesting that the circadian clock can integrate conflicting daily photic and non-photic cues. The present study investigated the daily expression of Fos-like immunoreactivity (Fos-ir) and light pulse-induced Fos-ir in the SCN, the intergeniculate leaflet (IGL) and the paraventricular thalamic nucleus (PVT) in calorie-restricted rats fed 2 h after the onset of light and in controls fed ad libitum. A daily rhythm of Fos-ir in the SCN was confirmed in control rats, with a peak approximately 2 h after lights on. At this time point (i.e. just prior to the feeding time), the level of SCN Fos-ir was lowered in calorie-restricted rats. Concomitantly, IGL Fos-ir was higher in calorie-restricted vs. control rats. In response to a light pulse during darkness, Fos-ir induction was found to be specifically (i.e. phase-dependently) lowered in the SCN and IGL of calorie-restricted rats. Observed changes of Fos-ir in the PVT were possibly related to the wake state of the animals. This study shows that repetitive non-photic cues presented in addition to a LD cycle affect the Fos expression in the circadian timing system.
Animals↗
Environmental control of the seasonal variations in the daily pattern of melatonin synthesis in the European hamster, Cricetus cricetus.
Nocturnal patterns of pineal melatonin concentrations were measured at hourly intervals in the European hamster, Cricetus cricetus, maintained under different natural or experimental environmental conditions. There were pronounced variations in the night peak of pineal melatonin both in the duration and the amplitude of the melatonin peak and in the onset and decline of melatonin synthesis. The duration of the melatonin peak increased proportionally with increased dark period. The amplitude increased abruptly from LD 16/8 to LD 15/9 and remained constant in all other photoperiods. The onset of synthesis started 6:00 hours after the onset of darkness in LD 16/8, 15/9, and 14/10, while it started 4:00 hours after dark onset in shorter photoperiods (LD 12/12 and 10/14). This result is opposite to that observed in the rat. The decline of synthesis was delayed as darkness increased and was directly related to lights on in long photoperiods, while it was endogenous in short photoperiods. Temperature, under a long photoperiod, also seems to be implicated in the regulation of the amplitude of the melatonin peak.
Animals↗
Effect of prolonged fasting and subsequent refeeding on free-running rhythms of temperature and locomotor activity in rats.
This study investigated the possible effect(s) of prolonged fasting and subsequent ad lib refeeding on the circadian organization of rats kept in constant darkness. Free-running rhythms of wheel-running activity and body temperature were studied in rats fasted during a 7-day interval followed with ad lib refeeding started either at subjective midday, i.e., CT6 (circadian time 6) or subjective midnight, i.e., CT18. Phase-shifts of temperature acrophases were similar to those of activity acrophases. During fasting, phase-shifts were phase-advanced (1 circadian h on the average) in most cases. During refeeding, they were mostly phase-delays (2 circadian h on the average) independently of the circadian time of refeeding, i.e., ad lib refeeding did not act as a Zeitgeber. In conclusion, prolonged fasting and subsequent refeeding induce opposite effects on the circadian organization.
Animals↗
Ventromedial nuclei of the hypothalamus are involved in the phase advance of temperature and activity rhythms in food-restricted rats fed during daytime.
Daily rhythms are synchronized to the light-dark cycle (LD) via a circadian clock located in the suprachiasmatic nuclei. A timed caloric restriction phase advances daily rhythms of body temperature and wheel-running activity in rats kept under LD. Because lesions of the ventromedial hypothalamic nuclei (VMH) prevent the fasting-induced changes in the day-night pattern of activity, it was hypothesized that the VMH might participate in the caloric restriction-induced phase changes. To test this hypothesis, rats with electrolytic or ibotenic acid lesions of VMH and control rats were fed 2 h after lights on 50% of ad lib food intake. During the preceding fed state, rats with electrolytic lesions of VMH displayed a less marked day-night difference in locomotor activity and a phase-advanced acrophase of temperature rhythm (2 h) compared to those of sham-operated rats. These effects were not found in fed rats with ibotenic lesions of VMH, suggesting that these effects of electrolytic lesions were due to disruption of undetermined fibers of passage. In response to a timed caloric restriction, the nocturnal peak of temperature rhythm was phase advanced by 7 h in sham-operated rats. Their day-night pattern of activity was also phase advanced towards the time of feeding. In both groups of food-restricted VMH-lesioned rats, the acrophase of temperature rhythm plateaued 3 h later than in sham-operated group. The phase advance of body temperature was, therefore, reduced to 4 h by ibotenic lesions of VMH and to 2 h by electrolytic lesions. Except for a feeding-associated component of activity expressed in control and VMH-lesioned rats, no significant change in day-night pattern of activity was detected in VMH-lesioned rats, either by electrolytic or ibotenic lesions. These results indicate that neuronal damage of the VMH limits the phase-advancing properties of a timed caloric restriction on the daily rhythms of temperature and locomotor activity.
Animals↗
Brown fat thermogenesis in rats fed high-fat diets enriched with n-3 polyunsaturated fatty acids.
OBJECTIVE: To examine the possible involvement of an increase in diet-induced thermogenesis from brown adipose tissue (BAT) in the n-3 polyunsaturated fatty acids (n-3 PUFA) induced limitation of the development of white fat pads during high-fat feeding. DESIGN: Rats fed for four weeks on a low-fat/high-carbohydrate diet (C group) or high-fat diet without n-3 PUFA (REF group), with eicosapentaenoic acid (EPA group), with docosahexaenoic acid (DHA group) or with a mixture of these two fatty acids (MIX group). MEASUREMENTS: Epididymal and retroperitoneal fat pad mass, BAT composition, Guanosine 5'-diphosphate (GDP) binding and uncoupling protein (UCP) content were measured in the five groups of rats. RESULTS: The masses of retroperitoneal and epididymal white fat pads were lower in the groups fed n-3 PUFA than in the C and REF groups. The total BAT GDP binding was 1.6 times higher in the MIX and EPA groups than in the REF group. The BAT from the EPA group presented an enrichment in mitochondria compared to the C and REF groups whereas the BAT from the DHA and REF groups presented a hyperplasia and an increase in thermogenic activity of the mitochondria compared to the C group. The higher thermogenic activity of BAT was observed in the MIX group and is due to hyperplasia and to an increase in thermogenic activity of mitochondria. CONCLUSIONS: n-3 PUFA induce a marked stimulation of BAT thermogenic activity without changes in the UCP content compared to a high-fat diet without n-3 PUFA. The mixture of EPA and DHA has the more pronounced effect while EPA and DHA seem to act in synergy on BAT thermogenesis via different mechanisms.
Adipose Tissue↗
Phase-advanced daily rhythms of melatonin, body temperature, and locomotor activity in food-restricted rats fed during daytime.
This study was performed to investigate possible effects of a timed caloric restriction on the light-dark (LD) synchronization of four biological rhythms pair-studied in the same animals. In Experiment 1, food-restricted rats kept under a photoperiod of 12 h light:12 h dark received 50% of previous ad libitum food 2 h after the onset of light. Their daily rhythm of pineal melatonin and rhythms of plasma melatonin and corticosterone were examined and compared to those of ad libitum control rats after 1 or 2 months of food restriction. A significant phase advance (about 2 h) was found for the pineal melatonin rhythm and for the daily onset of plasma melatonin. Timing of nocturnal peak of circulating corticosterone was unchanged, and a diurnal peak anticipated food presentation by about 2 h. In Experiment 2, effects of a timed caloric restriction under 12L:12D were studied on the expression of daily rhythms of body temperature and locomotor activity. To discriminate between the effects of timed meal feeding and those of the added caloric restriction, these rhythms were analyzed in food-restricted rats, as in Experiment 1, and were compared to those in sham-restricted rats, concomitantly fed twice more than food-restricted rats (i.e., a timed meal feeding without caloric restriction). Acrophase of the nocturnal peak of body temperature rhythm reached the greatest phase advance (7 h) in food-restricted rats, in which it was close to LD transition. The nocturnal component of locomotor activity rhythm also was markedly phase advanced (6 h) by caloric restriction, as indicated by wheel-running and general activity occurring form early afternoon to midnight. A smaller 4-h phase advance of the nocturnal peak of body temperature also was observed in sham-restricted rats, although the onset of locomotor activity rhythm apparently was unaffected by meal feeding and the end of activity rhythm was phase advanced by 2 h. These results indicate that timed caloric restriction is a potent phase-shifting agent that interacts with the LD cycle zeitgeber. This nonphotic stimulus phase advances melatonin, corticosterone, body temperature, and activity rhythms to different extents and thus suggests a change in the internal synchronization of the circadian system.
Animals↗
Lesion of the serotonergic terminals in the suprachiasmatic nuclei limits the phase advance of body temperature rhythm in food-restricted rats fed during daytime.
The daily rhythm of body temperature was recorded in control rats fed ad libitum and subsequently fed during daytime 50% of ad libitum food intake. Aside from the expression of a feeding-associated component, body temperature rhythm was phase advanced (7 h) by a timed caloric restriction; the new plateau of the acrophase of the nocturnal peak was close to the light-dark transition. A lesion of serotonergic (5-HTergic) terminals in the suprachiasmatic nuclei (SCN)-the endogenous circadian clock(s)-was performed by microinjection of the 5-HT neurotoxin 5,7-dihydroxytryptamine (5,7-DHT). During the ad libitum-fed state, the acrophase of body temperature rhythm was not modified by the 5,7-DHT treatment. In response to a timed caloric restriction, however, the phase advance of the nocturnal peak of body temperature rhythm was reduced by 2 h in rats with 5,7-DHT lesions as compared to that of sham-operated rats. Magnitude and day-night pattern of wheel-running activity between the two groups of rats also were analyzed. No intergroup difference was found in the amount of wheel-running activity prior to the time of feeding. Moreover, the phase advance of nocturnal component of locomotor activity rhythm observed toward the time of feeding in sham-operated rats was limited by 5,7-DHT treatment. It is concluded that the photic synchronization of body temperature rhythm does not depend on the 5-HTergic projection to SCN under ad libitum conditions. By contrast, the phase-advancing property of a timed caloric restriction on the daily rhythm of body temperature is mediated by a neuronal circuit involving the 5-HTergic projection to SCN. That the phase advance was not fully eliminated by 5,7-DHT treatment suggests that other pathways participate in this mediation.
Animals↗
Single-dose benzathine penicillin in infants at risk of congenital syphilis--results of a randomised study.
OBJECTIVE: To determine the efficacy of single-dose benzathine penicillin G in infants at high risk of congenital syphilis. DESIGN: Randomised study comparing benzathine penicillin with no therapy. SETTING: Peninsula Maternal and Neonatal Service, Cape Town. SUBJECTS: Asymptomatic infants born to mothers with untreated syphilis whose VDRL titre was 32 or more. OUTCOME MEASURES: The number of cases of congenital syphilis was determined by results of IgM Western blots and follow-up VDRL titres. RESULTS AND CONCLUSIONS: Of 8 patients followed up in the non-treatment group, 4 had congenital syphilis while 0/11 had the disease (P = 0.035) in the group receiving benzathine penicillin. Although the exact failure rate is unknown, benzathine penicillin is effective in preventing symptomatic congenital syphilis when administered to high-risk newborns.
Blotting, Western↗
Intergeniculate leaflet lesion and daily rhythms in food-restricted rats fed during daytime.
In control rats kept under light/dark cycle (LD) and fed during daytime 50% of ad lib food intake, the acrophase of temperature rhythm was 5 h phase-advanced, and plateaued close to the light/dark transition. The nocturnal pattern of locomotor activity rhythm was 6 h phase-advanced. By contrast, in food-restricted rats with electrolytic lesion of intergeniculate leaflet (IGL: IGLX group), there was only a 1 h phase-advance of the acrophase of temperature rhythm. Furthermore, except for a feeding-associated activity, the nocturnal pattern of activity of food-restricted IGLX rats remained unchanged. This demonstrates the involvement of IGL in the phase-advancing properties of a timed caloric restriction in LD.
Animals↗
Daily hypocaloric feeding entrains circadian rhythms of wheel-running and body temperature in rats kept in constant darkness.
Since high levels of physical activity are known to interact with the circadian system, we tested whether hyperactivity induced by hypocaloric feeding may facilitate the synchronizing effect of periodic feeding in rats in constant darkness. Wheel-running (WRR) and body temperature (BTR) rhythms were analyzed in rats fed daily 50% of ad libitum food intake. In addition to a feeding-associated component (FAC) expressed for both rhythms, WRR and BTR were phase-shifted towards the feeding time by 12.1 +/- 0.4 and 12.4 +/- 0.4 h, respectively. BTR and FAC of temperature merged into a single cosine-wave food-entrained rhythm (FER) of temperature. Similarly, WRR and FAC of activity merged into a unimodal FER of wheel-running. This indicates that daily hypocaloric feeding may synchronize circadian rhythms in rats.
Animals↗
Ventromedial hypothalamic lesions prevent the fasting-induced changes in day-night pattern of locomotor activity.
The time-course of day-night organization of running wheel activity during prolonged fasting was studied in rats, with or without electrolytic lesions in the ventromedial hypothalamus (VMH). For each individual, dates were referenced to the metabolic transition from lipid to protein utilization in late fasting; this was estimated by daily weighing. In fasted sham-operated controls, daytime activity increased progressively over the fast. This fasting-induced rise in diurnal activity was not due to daily handling, since it was observed also in non-handled (fasted) controls. The pattern of the increase in sham-operated rats differed between 2-hour periods (8-10 h to 18-20 h). The distribution of nocturnal activity was also modified during food deprivation: nocturnal activity in late fasting increased in the 20-22 h period and concomitantly decreased in the two 4-6 h and 6-8 h periods. By contrast, VMH lesions markedly limited and delayed the rise in diurnal running activity, irrespective of the 2-hour period. They prevented any significant change in nocturnal activity pattern over the fast. In fasted sham-operated rats, the data may be interpreted as a phase-advance of the nocturnal pattern of locomotor activity, concomitant with the increase of activity during daytime. These changes were suppressed by the VMH lesions. This suggests that the fasting-induced changes in the day-night pattern of locomotor activity are centrally mediated by a neuronal circuit involving the ventromedial hypothalamus.
Animals↗
Locomotor activity and utilization of energy reserves during fasting after ventromedial hypothalamic lesions.
The ventromedial hypothalamus (VMH) is known to be involved in the regulation of energy metabolism but it may also modulate locomotor activity. Since prolonged fasting is marked by a succession of changes in energy utilization and locomotor activity, it was hypothesized that VMH may be a critical link controlling mobilization of energy stores and/or behavioral changes in response to fasting. To test this, the changes in rate of body mass loss, body content in lipid and protein, and wheel-running activity were studied in fasted nonobese rats with VMH electrolytic lesions. Secondary effects of VMH obesity were ruled out by postoperative restricted feeding. During fasting, VMH lesions impaired neither the overall lipid mobilization nor the late rise in daily body mass loss, concomitant with the increase in net proteolysis. Despite that the onset of this late stage of fasting was significantly delayed in VMH vs. sham-operated rats (13 +/- 1 vs. 8 +/- 1 days, respectively), the final amount of reserve lipids (3 g) was closely similar in both groups: this is the first experimental evidence of the hypothesis of a lipidic set-point. These results indicate that VMH is not a critical link controlling the time-course of utilization of energy reserves. The increase in diurnal (and total) daily wheel-running observed in fasted sham-operated rats still occurred in fasted VMH rats but was significantly reduced and delayed. VMH nuclei and/or associated fibers are therefore involved in the fasting-induced rise in diurnal activity.
Animals↗
Involvement of corticosterone in the fasting-induced rise in protein utilization and locomotor activity.
During fasting, most of the energy is derived from lipids whereas proteins are efficiently spared. However, there is a late rise in net protein utilization. Fasting is also associated with an increase in locomotor activity. Because the plasma corticosterone level increases concomitantly with these metabolic and behavioral changes, the involvement of corticosterone has been hypothesized. To test this, the net protein utilization and locomotor activity were investigated in fasted adrenalectomized (Adx) rats, with or without replacement with corticosterone, and in fasted intact rats treated with RU486, an antagonist of type II glucocorticoid receptors. During the phase of fasting characterized by protein sparing, urine nitrogen loss was further reduced in Adx rats and in RU486-treated controls compared with intact rats and with Adx rats with corticosterone replacement: this indicates a catabolic effect of corticosterone through type II receptors. In the last phase of fasting, the rise in net protein breakdown was suppressed in Adx rats and restored by corticosterone replacement. The increase in locomotor activity induced by fasting in controls was suppressed in Adx and restored by corticosterone replacement. This rise in running activity was still present in RU486-treated rats. In conclusion, this study shows that corticosterone plays a critical role in the changes of both protein catabolism and locomotor activity during prolonged fasting.
Adipose Tissue↗
Stimulation of brown adipose tissue activity in tumor-bearing rats.
Despite anorexia, cancer development is frequently accompanied by an increase of energy expenditure. Considering the pivotal role played by brown adipose tissue (BAT) in the energy metabolism of small mammals, we investigated the functional and compositional modification in BAT of anorexic tumor-bearing (Yoshida sarcoma) and pair-fed control rats. BAT thermogenic activity (assessed by maximal mitochondrial GDP binding) was 1.8-fold greater in tumor-bearing rats than in controls, while the thermogenic capacity (assessed by measurement of uncoupling protein) was unchanged. This suggests that tumor bearing had induced an unmasking of uncoupling protein sites. BAT hypertrophy and hyperplasia, characteristic of full-fledged BAT activation, did not occur. The mitochondrial oxidative capacity of BAT (assessed by cytochrome c oxidase activity) was 1.6-fold lower in tumor-bearing than in control rats. The main compositional modification observed in BAT of tumor-bearing rats was an increase in the saturation of cardiolipin fatty acids. These results suggest that the BAT stimulation induced by tumor bearing after 10 days is almost exclusively functional and that the tissue development is limited, probably by anorexia. However, a suppressive effect of anorexia inhibition by tumor bearing cannot be excluded.
Adipose Tissue, Brown↗
Search for rhythmicity during hibernation in the European hamster.
Temporal patterns of hibernation were studied by continuous monitoring of body temperature by radiotelemetry over 6 months in European hamsters, Cricetus cricetus, at constant temperature and photoperiod. Entrances into hibernation occurred mostly at the end of the night (0000-0800 hours), while arousals were randomly distributed between day and night. This is at variance with a control of bout duration by a clock with a period of 24 h. Consequently, the timing of entrances implies a phase-resetting of the circadian clock on each arousal. Persistence of circadian rhythmicity with a period different from 24 h during deep hibernation was investigated examining whether the durations of torpor bouts were integer multiples of a constant period. A non-parametric version of the classical contingency test of periodicity was developed for this purpose. Periods ranging from 21 to 29 h were tested. Nine animals out of ten showed at least one significant period in this range (P < 0.01), either below 24 h (21.8 +/- 0.5 h, n = 4) or above (27.3 +/- 0.5 h, n = 7). However, we have found a theoretical model of bout durations for which the contingency test of periodicity sometimes gives false significant results. This indicates that the power of the test is weak. With this reservation our results suggest that a circadian oscillator controls the duration of a bout of hibernation, which would occur after an integer, but variable and possibly temperature-dependent number of cycles.
Animals↗
Body protein and lipid deficit in tumour-bearing rats in relation to age.
Cancer cachexia is among the most dramatic situations of depletion in body energy reserves. To ascertain whether the pattern of body composition alteration during tumour development is influenced by aging as in uncomplicated starvation, we compared the difference of body composition between Yoshida sarcoma bearing rats and young (200 g, 7 weeks) and adult (400 g, 13 weeks) control rats. After the same duration of tumour bearing, mass and composition of tumours were similar in adult and young rats, indicating that they are independent of host age. Food intake decreased to a remarkably similar value in both young and adults. Body water content was elevated in hosts of both ages. The relative deficit of body lipid vs controls was similar for both, the absolute lipid deficit being therefore larger in adult than in young tumour-bearing rats (14.3 +/- 4.4 g vs 6.8 +/- 0.9 g; P < 0.01). In contrast, there was a relatively larger deficit of body protein in young rats. Paradoxically, these rats still maintained a positive nitrogen balance whereas this balance was negative in adult tumour-bearing rats. In conclusion, as previously shown in uncomplicated undernutrition, the anorexia induced by Yoshida sarcoma development is still associated with some protein accretion in young rats whereas cachexia develops in adults.
Aging↗