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A Malan

Publications and source records attributed to A Malan.

At least 19 recordsLinked to original sources
PubMed2003

Photoperiod differentially regulates clock genes' expression in the suprachiasmatic nucleus of Syrian hamster.

The suprachiasmatic nuclei (SCN) contain the master circadian pacemaker in mammals. Generation and maintenance of circadian oscillations involve clock genes which interact to form transcriptional/translational loops and constitute the molecular basis of the clock. There is some evidence that the SCN clock can integrate variations in day length, i.e. photoperiod. However, the effects of photoperiod on clock-gene expression remain largely unknown. We here report the expression pattern of Period (Per) 1, Per2, Per3, Cryptochrome (Cry) 1, Cry2, Bmal1 and Clock genes in the SCN of Syrian hamsters when kept under long (LP) and short (SP) photoperiods. Our data show that photoperiod differentially affects the expression of all clock genes studied. Among the components of the negative limb of the feedback loop, Per1, Per2, Per3, Cry2 but not Cry1 genes show a shortened duration of their peak expression under SP compared with LP. Moreover, mRNA expression of Per1, Per3 and Cry1 are phase advanced in SP compared with LP. Per3 shows an mRNA peak of higher amplitude under SP conditions whereas Per1 and Per2 peak amplitudes are unaffected by photoperiod changes. Bmal1 expression is phase advanced without a change of duration in SP compared with LP. Furthermore, the expression of Clock is rhythmic under SP whereas no rhythm is observed under LP. These results, which provide further evidence that the core clock mechanisms of the SCN integrate photoperiod, are discussed in the context of the existing molecular model.

ARNTL Transcription Factors↗
PubMed2001

The circadian clock, light/dark cycle and melatonin are differentially involved in the expression of daily and photoperiodic variations in mt(1) melatonin receptors in the Siberian and Syrian hamsters.

Mechanisms underlying the daily and photoperiodic variations in mt(1) melatonin receptors were investigated in the pars tuberalis (PT) and suprachiasmatic nuclei (SCN) of Siberian and Syrian hamsters. Whatever its daily profile, melatonin receptor density was strongly increased in both structures and species after constant light exposure or pinealectomy, and decreased after a single melatonin injection, indicating melatonin involvement in the daily regulation of the receptor protein. This was confirmed by a strong inverse correlation between melatonin binding capacity and plasma melatonin concentration. In contrast, regulation of mt(1) mRNA appeared more complex. The circadian clock, the light/dark cycle and melatonin are all implicated in mt(1) gene daily fluctuations, but the extent of their involvement depends upon the structure and the species studied. The photoperiodic decrease in melatonin receptor density observed in short photoperiod (PT of the two hamster species and Syrian hamster SCN) seems to be the consequence of a long-term mt(1) gene repression induced by the lengthening of the melatonin peak. Altogether, these results show that during daily variations, mt(1) melatonin receptor mRNA and protein are differentially regulated, while at the photoperiodic level, the mt(1) protein status depends on mRNA transcription.

Animals↗
PubMed2000

Potentiation effect of vasopressin on melatonin secretion as determined by trans-pineal microdialysis in the Rat.

The mammalian pineal gland is known to receive a noradrenergic innervation originating from the superior cervical ganglion which corresponds to the primary regulatory input for melatonin synthesis. However, many peptidergic fibers containing peptides such as vasopressin and oxytocin have also been found in the rat pineal gland. The present study was performed to investigate the possible role of vasopressin and oxytocin on melatonin secretion in vivo. Therefore, both neuropeptides were delivered for 2 h through a trans-pineal microdialysis probe directly into the gland at different times during the nocturnal phase of the light:dark cycle. At the same time pineal dialysates were collected continuously. Melatonin concentrations were measured by radioimmunoassay. Melatonin synthesis potentiation was achieved when vasopressin was infused locally in the pineal, during the onset of nocturnal melatonin secretion. In order to assess the possible role of a physiological increase of endogenous circulating vasopressin on pineal metabolism, melatonin synthesis was recorded in the same animals before and after a prolonged dehydration period. Night time melatonin concentration was increased after the water deprivation vs control conditions. Contrary to that, oxytocin seems not to affect pineal metabolism in the rat since no significant change was observed on melatonin secretion in response to a local oxytocin infusion. These results show that vasopressin can modulate melatonin synthesis in the rat pineal whereas no effect was obtained with oxytocin, at least under the present experimental conditions.

Animals↗
PubMed2000

Day-night pattern of energy expenditure and body temperature in cachectic tumour-bearing rats.

The implication of an increase in energy expenditure in cancer cachexia, which seems to be related to the type of tumour, remains unclear. We therefore investigated the energy metabolism and body temperature in anorectic and cachectic rats bearing the Yoshida sarcoma (TB), in comparison with pair-fed (PF) and ad-libitum fed (AL) control rats. The resting energy expenditure was higher in the TB than in the two control groups when corrected for the modifications of body composition. However, the total energy expenditure did not differ between the TB and the AL, presumably because of the drop of activity in TB. There was a temporal distribution of differences in energy expenditure with higher energy expenditure in TB than in AL during the diurnal phase and a lack of difference during the nocturnal phase. The TB presented a fever, which was limited to the diurnal period. Moreover, the acrophase of the body temperature rhythm was delayed in the TB. These results highlight the circadian effects of tumour development on the energy metabolism of the host and hint to the possible implication of cytokines.

Adipose Tissue↗
PubMed1999

Interindividual differences in the pattern of melatonin secretion of the Wistar rat.

In vivo trans-pineal microdialysis was performed in male Wistar rats maintained under a 12 hr light:12 hr dark (LD 12:12) cycle. Collected dialysates were assayed by radioimmunoassay for melatonin concentrations. A non-linear regression was fitted through the obtained datapoints to determine the time points at which a 50% increase (IT50) and decrease (DT50) of the nocturnal melatonin peak were reached. In a first experiment, the nocturnal melatonin profiles of four animals were determined throughout 5 consecutive days. In a second experiment, we analysed the melatonin profiles during the night in rats originating from three different breeding colonies (Dépré Harlan, and Iffa-Cŕedo). A low intraindividual variability was found on the phase markers IT50 and DT50, as on peak duration of melatonin rhythms estimated over 5 subsequent days in the same animal. In contrast, animals showed a large interindividual variability in their profile phase markers and the values were dependent on the origin of the breeding colony. Each rat colony was characterized by early or late IT50 and DT50 as long or short peak length. It is concluded from experiment 1 that the melatonin rhythm is a very stable circadian marker. Nevertheless, great caution must be taken in the choice of animal groups while studying circadian rhythms due to the large interindividual variability observed in experiment 2. Therefore, as the technique allows the use of the animal as its own control, the present study demonstrated that the use of the microdialysis technique is of interest in studies on the circadian system.

Animals↗
PubMed1999

Organization of rat circadian rhythms during daily infusion of melatonin or S20098, a melatonin agonist.

Daily administration of melatonin or S20098, a melatonin agonist, is known to entrain the free-running circadian rhythms of rats. The effects of the duration of administration on entrainment were studied. The animals demonstrated free-running circadian rhythms (running-wheel activity, body temperature, general activity) in constant darkness. Daily infusions of melatonin or S20098 for 1, 8, or 16 h entrained the circadian rhythms to 24 h. Two daily infusions of 1 h (separated by 8 h) entrained the activity peak within the shorter time interval. The entraining properties of melatonin and S20098 were similar and were affected neither by pinealectomy nor by infusion of 1- or 8-h duration. However, with 16-h infusion, less than half of the animals became entrained. Once entrained, the phase angle between the onset of infusion and the rhythms (onset of activity or acrophase of body temperature) increased with the duration of infusion. Before entrainment, the free-running period increased with the duration of infusion, an effect that was not predictable from the phase response curve.

Acetamides↗
PubMed1999

Photoperiodic control of the rat pineal arylalkylamine-N-acetyltransferase and hydroxyindole-O-methyltransferase gene expression and its effect on melatonin synthesis.

Photoperiodic changes of pineal melatonin (MEL) profile are accompanied by parallel changes of arylalkylamine-N-acetyltransferase (AA-NAT) activity. In the present study, the authors investigated, for the first time, whether two other important variables of pineal metabolism, AA-NAT and hydroxyindole-O-methyltransferase (HIOMT) gene expression, also may be affected by the photoperiod. Evening rises in AA-NAT and HIOMT mRNA and in circulating MEL occurred concomitantly with an increased delay from dark onset as scotophase shortened. On the opposite, the morning declines of all three variables occurred with different kinetics but were locked to light onset. These observations demonstrate that the daily rhythms in AA-NAT and HIOMT gene expression are modulated by the photoperiod and bring further evidence in favor of nor adrenaline as the possible link between the endogenous clock and MEL. Interestingly, the duration of the nocturnal peak in HIOMT mRNA was positively correlated with HIOMT activity. In conclusion, this study adds two important links to the chain of mechanisms involved in the photoperiodic control of pineal metabolism. First, photoperiodic modulation of the MEL rhythm primarily results from changes in the AA-NAT gene expression. Second, the photoperiodic regulation of HIOMT activity occurs at the transcriptional level.

Acetylserotonin O-Methyltransferase↗
PubMed1998

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗