Biomedical subjects

M Saboureau

Publications and source records attributed to M Saboureau.

At least 19 recordsLinked to original sources

PubMed2006

Melatonin in the multi-oscillatory mammalian circadian world.

In mammals, the complex interaction of neural, hormonal, and behavioral outputs from the suprachiasmatic nucleus (SCN) drives circadian expression of events, either directly or through coordination of the timing of peripheral oscillators. Melatonin, one of the endocrine output signals of the clock, provides the organism with circadian information and can be considered as an endogenous synchronizer, able to stabilize and reinforce circadian rhythms and to maintain their mutual phase-relationship at the different levels of the circadian network. Moreover, exogenous melatonin, through an action on the circadian clock, affects all levels of the circadian network. The molecular mechanisms underlying this chronobiotic effect have also been investigated in rats. REV-ERB alpha seems to be the initial molecular target.

Animals↗

PubMed2002

The chronobiotic properties of melatonin.

In mammals, the exact role of melatonin (Mel) in the circadian timing system remains to be determined. However, exogenously administered Mel, as reported in the present mini-review, has been shown to affect the circadian clock. The sites and mechanisms of action involved in this "chronobiotic" effect of Mel have begun to be characterized. The suprachiasmatic nuclei (SCN) appear to be an important site for the entrainment effect of Mel and the presence of Mel receptors appears to be a prerequisite. However, the pharmacological dose of Mel needed to entrain circadian rhythms means that very probably other sites and mechanisms also play a role.

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↗

PubMed1999

Role of the thalamic intergeniculate leaflet and its 5-HT afferences in the chronobiological properties of 8-OH-DPAT and triazolam in syrian hamster.

The 5-HT(1A/7) receptor agonist 8-hydroxy-2-[di-n-propylamino]-tetralin (8-OH-DPAT) has chronobiological effects on the circadian system and, in the Syrian hamster, it is known that serotonergic (5-HT) projections connecting the median raphe nucleus to the suprachiasmatic nuclei (SCN) of the hypothalamus are a prerequisite for the expression of 8-OH-DPAT-induced phase advance of locomotor activity rhythm. We examined the possible involvement of the thalamic intergeniculate leaflet (IGL) in the phase-shifting properties of 8-OH-DPAT injections at CT7. Bilateral electrolytic lesions of the IGL blocked phase-shift responses to 8-OH-DPAT of the activity rhythm. Phase changes induced by injections of 8-OH-DPAT at CT7 and triazolam (Tz), a short-acting benzodiazepine, at CT6 were also studied after bilateral chemical lesion of the 5-HT fibres connecting the dorsal raphe nucleus (DR) to IGL. Destruction of 5-HT fibres within the IGL blocked the phase-shift response to Tz, but not the phase-shift response to 8-OH-DPAT. In conclusion, (a) IGL is essential for the phase-shifting effect of peripheral 8-OH-DPAT injections; (b) 5-HT fibres connecting DR to IGL are necessary for the expression of the phase-shifting effect of Tz but not of 8-OH-DPAT.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1999

Circannual reproductive rhythm in the European hamster (Cricetus cricetus): demonstration of the existence of an annual phase of sensitivity to short photoperiod.

In the European hamster (Cricetus cricetus) short photoperiod (SP) is responsible for the transition between the breeding and the resting season and data obtained previously suggest that a circannual "clock" drives the annual rhythm of reproduction. This hypothesis implies the existence of a SP-sensitive phase of the circannual system that occurs independently of the photoperiodic regime perceived by the animals after their arousal from hibernation at the end of March. In control animals kept outside, testicular atrophy occurs in August. When the animals were transferred from outdoors to controlled SP conditions (LD 10:14 and ambient temperature Ta = 18+/-2 degrees C), immediately (Group II) or 2, 4, 6 wk after capture (Groups IV, V, VI, respectively), sexual arrest occurs at the same time between mid-June and mid-July. In the other groups, transfer from outdoors to SP either after 6, 8, 10, 12 or 14 wk (Groups VI, VII, IX, X, XI, respectively) after capture, is followed directly within 4 wk by the gonadal atrophy. When SP was applied from the beginning of August (Group XII) gonadal atrophy was observed after only 2 wk. In this last group, however, the rapid involution is the consequence of the already initiated decline in sexual activity induced by the short daylengths from July. When comparing the effect of SP in two different ambient temperatures (Ta: 18+/-2 degrees C vs 7+/-2 degrees C), immediately (Groups II vs III), 8 (Groups VII vs VIII) or 16 (Groups XII vs XIII) wk after capture, it appears that low temperature does not affect the physiological process described above. In the European hamster, after the gonadal regrowth at the end of hibernation, the animals do not need to experience increasing long days to react against SP. Gonadal inhibition is induced when, following our hypothesis, SP coincides with an endogenous period of sensitivity that extends from mid-May to at least July-August. The present findings complement and extend earlier evidence to support the existence of an endogenous circannual control of seasonal reproduction in the European hamster.

Animals↗

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↗

PubMed1998

In Syrian hamsters, 5-HT fibres within the suprachiasmatic nuclei are necessary for the expression of 8-OH-DPAT induced phase-advance of locomotor activity rhythm.

8-Hydroxy-2-[di-n-propylamino]-tetralin) (8-OH-DPAT), a 5-HT1A/7 receptor agonist, has a chronobiological effect on the circadian system. To identify how the 8-OH-DPAT exerts this effect, we specifically destroyed the serotonergic (5-HT) fibres connecting the median raphe nuclei (RN) to the suprachiasmatic nuclei (SCN) of the hypothalamus by using microinjections of a neurotoxin 5,7-dihydroxytryptamine into the SCN. After administration of 8-OH-DPAT (0.1 ml, 5 mg/kg) at circadian time 7, the control and the 'partially-lesioned' animals showed a large phase-advance whereas in the 'well-lesioned' hamsters the phase-advances were significantly reduced or absent. The present study demonstrates that, in the Syrian hamster, the 5-HT fibres connecting the RN to the SCN are essential for the phase-shifting action of peripheral 8-OH-DPAT injections, and that the drug does very probably not exert its chronobiological effect directly onto SCN neurons but through receptors localized on median raphe nucleus neurons.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1996

Phase-shifting effect of 8-OH-DPAT, a 5-HT1A/5-HT7 receptor agonist, on locomotor activity in golden hamster in constant darkness.

The present results show that under constant darkness the endogenous circadian pacemaker located in the suprachiasmatic nuclei can be affected by administration of 8-hydroxy-2-[di-n-propylamino] tetralin (8-OH-DPAT), a well known 5-HT1A/5-HT7 receptor agonist. A single i.p. injection (0.1 ml) with 8-OH-DPAT (5 mg/kg) induced significant phase-advances of hamster locomotor activity at circadian time (CT) 6 and 8 and a significant phase-delay at CT11. Saline injections by themselves induced a significant phase-advance at CT10-11. The dose-response curve for 8-OH-DPAT showed a maximal phase-shifting effect for doses of at least 2.5 mg/kg at CT8. Thus, in golden hamsters. (1) 8-OH-DPAT has a chronobiological effect with sensitivity depending upon the circadian time of injection, and (2) a single saline injection is able to induce regular phase-advances at the end of the subjective day (CT10-11).

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1996

Water turnover evaluated by the tritiated water method and by the nutritional method in European hedgehog (Erinaceus europaeus L.).

The total body water (TBW), the fractional water turnover rate (WTR), and the water flux rates (WFR) were studied for the first time by the tritiated-water method in 10 hedgehogs under laboratory conditions during the year. To validate this method, we compared the result to the nutritional method. The TBW varied inversely with body mass (BM) during both the active and the hibernation periods. The WTR varied from 16% to 21% during the hibernation period and after the reproduction. The higher values (from 22% to 26%) were recorded during the reproduction period and during the preparation for hibernation. The same variations in WFR were recorded during the active and hibernation period. The net gain or loss of water followed the gain and loss of BM. The tritiated water (THO) method has been validated by the fact that the same variations in WFR during each month have been measured by the THO method and the nutritional method. Moreover, the THO method can be used to estimate the changes in energy metabolism of hedgehogs in relation with the seasons.

Analysis of Variance↗

PubMed1995

Protein and lipid utilization during fasting with shallow and deep hypothermia in the European hedgehog (Erinaceus europaeus).

We investigated whether the relative contributions of body protein and lipid reserves differ according to the level of energy expenditure in fasting animals. Protein and lipid utilization was therefore quantified and compared in hedgehogs which fasted with shallow and deep hypothermia, i.e. by exposure at 5 or 20 degrees C ambient temperature. Body composition was determined for every 150-g decrease in mass throughout the experiment, allowing the calculation of regression lines between body mass (independent variable, x) and body composition (dependent variable, y: water, protein, neutral lipids, phospholipids and cholesterol). There were highly significant (P < 0.001) linear decreases in all body components with decreasing body mass in both groups of hedgehogs. Neutral lipids were the main component of the total body mass loss (54%) in fasted animals with shallow and deep hypothermia, percentages of water (26-30%) and protein (10-11%) being lower, and those of phospholipid and cholesterol negligible (< 0.5%). In spite of different levels in energy expenditure (2.54 and 1.07 W.kg-1 in shallow- and deep-hypothermal fasting hedgehogs, respectively), the energy sources were identical in both groups, neutral lipid being the main fuel (91-92%) and body protein accounting for the remainder (8-9%). Prolonged fasting with shallow and deep hypothermia were marked by low alaninemia and glycemia, while plasma free fatty acids and beta-hydroxybutyrate were elevated.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Plasma lipid transport in the hedgehog: partial characterization of structure and function of apolipoprotein A-I.

Apart from exhibiting the presence of lipoprotein [a] in its plasma, another interest of the European hedgehog in lipoprotein research lies in the quantitative prominence of a complex spectrum of high density lipoproteins (HDL) and very high density lipoproteins (VHDL) as cholesterol transporters in plasma (Laplaud, P. M. et al. 1989. Biochim. Biophys. Acta. 1005: 143-156). We, therefore, initiated studies in the field of reverse cholesterol transport in the hedgehog. As a first step, we characterized apolipoprotein A-I (apoA-I), the main protein component of hedgehog HDL and VHDL. Proteolytic cleavage of apoA-I (M(r) approx. 27 kDa) using two different enzymes resulted in two sets of peptides that were subsequently purified by high performance liquid chromatography, and that allowed us determination of the complete protein sequence. Hedgehog apoA-I thus consists of 241 amino acid residues and exhibits an overall 58% homology to its human counterpart, i.e., the lowest value observed to date among mammalian species. However, it retained the general organization common to all known apoA-Is, i.e., a series of amphipathic helical segments punctuated by proline residues. Circular dichroism experiments indicated a helical content of approx. 45%, increasing to approx. 58% in the presence of lecithin unilamellar liposomes. Apart from other differences, amino acid composition analysis shows that hedgehog apoA-I contains four isoleucine residues, while this amino acid is totally absent from the corresponding protein in higher mammals. Polyclonal antibodies raised against hedgehog apoA-I failed to detect any cross-reactivity between the animal and human proteins, although comparative prediction of the respective antigenic structures using the Hopp-Woods algorithm indicated that several potentially antigenic sites may occur in similar regions of the protein. Finally, hedgehog apoA-I was shown to be able to activate lecithin:cholesterol acyl transferase, although it was 4 to 5 times less efficient in this respect than the human protein.

Amino Acid Sequence↗

PubMed1994

An attempt to correlate brain areas containing melatonin-binding sites with rhythmic functions: a study in five hibernator species.

High affinity melatonin-binding sites have been described, by means of autoradiography with 2-125I-melatonin as the ligand, in more than 60 brain areas of about 20 mammalian species, with dramatic variations in the nature and number of labelled structures among the different species studied. As melatonin is involved in the synchronization of biological rhythms, we have tried to correlate the brain areas containing melatonin-binding sites with some rhythmic functions typical of given species. Therefore, we have studied the location of melatonin-binding sites in the complete brain of five long-day breeders with hibernation cycles, viz. one insectivore and four rodents. With the exception of the suprachiasmatic nuclei and the pars tuberalis of the pituitary, both of which contain binding sites in all five species, few reactive structures are common, even among species from the same family, e.g. the edible dormouse and the garden dormouse.

Animals↗

PubMed1994

Are the annual reproductive and body weight rhythms in the male European hamster (Cricetus cricetus) dependent upon a photoperiodically entrained circannual clock?

Most of the data obtained so far on the European hamster (Cricetus cricetus) suggest direct photoperiodically driven seasonal changes in sexual activity and body weight. The results of the present long-term study support the hypothesis that these annual changes are the expression of photoperiodically driven endogenous circannual rhythms. When subjected following capture (April-May) to constant conditions of long photoperiod (LP) and constant temperature a large number of the European hamsters present, in September-December, complete gonadal atrophy associated with a decrease in body weight. A sexual reactivation as well as an increase in body weight are observed in the same animals between January and April. Of the six animals that survived long enough, two only presented partial gonadal atrophy during the second year. These observations clearly demonstrate that the decline in sexual activity in subjective autumn does not require a decrease in photoperiod, at least in the first year. Theoretically, the observed rhythms, if circannual in nature, would be generated by a self-sustained annual oscillator (circannual clock) able to function in the absence of a photoperiodic input. Pinealectomy makes animals unable to detect or measure photoperiodic information. Of the six European hamsters tested (pinealectomized in June and then kept continuously under LP), five showed clear annual rhythms in body weight and reproductive capacities for two consecutive years. Clearly endogenous annual rhythms were expressed in these conditions. To be entrained to a 1-year period, such a circannual clock should, however, be able to react to either LP and/or to short-photoperiod (SP), at least at certain periods of the annual cycle. In animals exposed to LP in August or October, after gonadal atrophy had been established by exposure to natural SP, gonadal regrowth started in December or January, about 2 to 3 months earlier than in animals kept outside or in experimental SP. With the same experimental conditions, exactly the same results were obtained in pinealectomized animals; thus stimulatory effect of LP or LP-induced phase advance of the circannual clock can be excluded. The absence of the SP information would then induce such reaction. In animals kept under constant LP and temperature following capture, however, pinealectomy in January--when all animals are sexually active--induces gonadal atrophy within--weeks. This clearly demonstrates that LP is stimulatory at this time of the subjective year.

Animals↗

PubMed1994

Growth-related changes in testicular mass and plasma testosterone concentrations in long-finned pilot whales, Globicephala melas.

Blood samples and testes were collected from long-finned pilot whales (Globicephala melas) off the Faroe Islands at irregular intervals over a period of 3 years (July 1986-December 1989). Changes in testis mass (n = 674) and plasma testosterone concentrations (n = 214), measured by radioimmunoassay, were examined with respect to age, bodylength and bodymass of the animals. Corresponding to a rapid testicular growth (from 0.25 kg up to 1.9 kg), puberty occurred in male pilot whales of 4.6-5.7 m in bodylength, 1.2-1.9 tonnes in bodymass and 11-22 years of age. Changes in plasma testosterone concentrations confirmed this result, with very low values (< 2 ng ml-1) in immature animals (testis mass < 0.2 kg), followed by a sharp increase (from 2 to 29 ng ml-1) during the pubertal period, and the maintenance of high concentrations with large variability (> 1.5 ng ml-1 to 14 ng ml-1) in mature males. Testosterone concentrations were significantly correlated with testis mass (P < 0.001), but not with bodylength or age, and very large individual variations were observed in mature males. The average age, length and mass at the attainment of sexual maturity were estimated at 16.99 +/- 0.30 years, 5.162 +/- 0.013 m and 1.403 +/- 0.005 tonnes, respectively.

Animals↗

PubMed1993

Effects of bilateral superior cervical ganglionectomy on thyroid and gonadal functions in the edible dormouse Glis glis.

1. The annual profiles of plasma thyroid-stimulating hormone (TSH), thyroxine (T4), luteinizing hormone (LH) and testosterone (T) concentrations in control and ganglionectomized (SCGx) dormice were analyzed to determine whether the pineal gland affects thyroid-gonadal interactions in response to the seasonal influence of environmental factors. 2. Dormice ganglionectomized in September, around the time of prehibernation when hormonal activity is minimal had significantly disturbed annual cycles of plasma T4, LH and T, while the TSH cycle was unchanged. 3. SCGx performed after breeding season (June), only affected the T4 variations, while the T and LH titers were similar to those of controls. 4. We conclude that the annual cycles of T4 and testosterone are controlled by the sympathetic nervous system via the superior cervical ganglion which innervates both the pineal gland and the thyroid. 5. During the start of seasonal gonadal activity, which is strongly dependent on thyroid-gonadal interactions, the inhibitory action of the pineal gland on the neuroendocrine thyroid axis, or most probably a direct inhibition of the thyroid by the sympathetic innervation from SCG, might influence the timing of the reproduction cycle. 6. The lack of thyroid-gonadal interaction at the end of the breeding season suggests that the thyroid disturbance caused by ganglionectomy in June does not cause gonadal perturbation at this time.

Animals↗

PubMed1993

Differential seasonal regulation of melatonin receptor density in the pars tuberalis and the suprachiasmatic nuclei: a study in the hedgehog (Erinaceus europaeus, L.).

Using quantitative autoradiography, we have studied the seasonal changes of high affinity melatonin receptor density in both the SCN and PT of the hedgehog, a seasonal breeder and an hibernator. Animals in 3 different physiological states were studied: sexually active animals, and sexually inactive animals during the hibernation period, being then either euthermic or hypothermic. In sexually active animals, Bmax were 75.8 +/- 7.1 fmol/mg protein in PT and 9.1 +/- 0.5 fmol/mg protein in SCN; and Kd values were: 94 +/- 22 pM in the PT and 101 +/- 15 pM in the SCN. This specific binding was strongly decreased in the PT of sexually inactive animals. Moreover, this decrease was significantly stronger in hypothermic than in euthermic hedgehogs. Saturation studies and Scatchard analysis revealed that the observed decrease in the PT resulted from change in the Bmax but not in the Kd, Bmax values being respectively 56.4 +/- 5.9 and 29.5 +/- 1.9 fmol/mg protein in euthermic and hypothermic sexually at rest animals. In none of the different physiological states, did the density of melatonin receptors of the SCN show any changes, Bmax values being respectively 9.8 +/- 0.5 and 9.8 +/- 0.4 fmol/mg protein in euthermic and hypothermic sexually at rest animals. This shows for the first time a tissue-specific regulation of melatonin receptor density occurring in the PT but not in the SCN. Furthermore, this decrease of binding in the PT is correlated with both sexual inactivity and hibernation period. This strongly suggests that the mediation of the photoperiodic effect on seasonal functions like seasonal hypothermia and reproduction involves an effect of melatonin on the PT rather than on the SCN.

Animals↗

PubMed1993

Effect of light entrainment and temperature on the reproductive cycle in the male hedgehog (Erinaceus europaeus).

The role of photoperiod in the entrainment and synchronization of the reproductive cycle of male hedgehogs, seasonal breeders and hibernating mammals, was investigated. Groups of adult hedgehogs were either maintained outdoors (controls, n = 6) or submitted to accelerated 6-month artificial light regimens under constant ambient temperatures (20 +/- 2 degrees C versus 5 +/- 1 degrees C) in light-proofed rooms. The daily duration of light was varied sinusoidally to produce an amplitude change from 8 h (winter solstice) to 16 h (summer solstice) during the 6-month light cycle. Animals were transferred from outdoors to a high ambient temperature (20 +/- 2 degrees C) and submitted to accelerated 6-month light regimens at two times of the year: from winter solstice (Group 1, n = 14) with increasing daylengths (from 8 to 16 h) and from summer solstice (Group 2, n = 8) with decreasing daylengths (from 16 to 8 h). The light regimens were then reversed for Groups 1 and 2. After the first 6-month cycle, the animals in Group 1 were allocated to two groups and maintained under the same initial light regimen but submitted to two ambient temperatures: Group 1 (n = 7) was maintained at 20 +/- 2 degrees C and Group 3 (n = 7) was transferred to a cold environment (5 +/- 1 degrees C). In control and experimental animals, testicular volume was estimated and blood samples were obtained twice a month to measure plasma testosterone and LH concentrations by radioimmunoassay.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗

PubMed1992

Seasonal changes in thyroid-gonadal interactions in the edible dormouse, Glis glis.

This study was conducted to determine changes in thyroid-gonadal interaction in the edible dormouse during the phase of the annual cycle that corresponds to the end of the breeding season (from June to September). We evaluated intra-hypothalamic luteinizing hormone-releasing hormone (LHRH) content, and plasma concentrations of luteinizing hormone (LH), testosterone, thyroid-stimulating hormone (TSH) and thyroxine (T4) in three groups of dormice: (1) controls; (2) dormice receiving sufficient T4 supplementation to maintain June levels in control animals until September, thus counteracting the seasonal reduction of T4 that normally begins in July; and (3) thyroidectomized dormice. The effect of thyroidectomy was only detectable in June, when plasma T4 concentration in the control group was maximal, and consisted of a significant decrease in plasma testosterone levels. This provides strong support for the hypothesis that thyroid function positively influences gondal function during the breeding season. The T4 supplementation resulted in a decrease in hypothalamic LHRH concentration, suggesting that an increased LHRH release led to the observed stimulated hypophyseal secretion of LH in June and September and the increased circulating testosterone levels in September. There was no detectable effect in July and August. These results show that thyroid axis activation of the hypothalamic-pituitary-gondal system is only possible during certain phases of the annual cycle, particularly evidenced here during the breeding season. They also reinforce our conclusions drawn from the thyroidectomy results. Conversely, the summer testicular regression which normally occurs after the breeding season is no longer controlled by plasma T4 levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗