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Biomedical subjects

M Jouvet

Publications and source records attributed to M Jouvet.

At least 73 records · Page 4Linked to original sources

Hypothalamic injection of prolactin or its antibody alters the rat sleep-wake cycle.

Several studies have suggested an interaction between prolactin and the sleep-wake cycle. In this study ovine prolactin (oPRL) and anti-prolactin antibody were microinjected into the rat dorsolateral hypothalamus, which contains prolactin-like immunoreactive neurons. Results indicate that during the light period, prolactin injection induced an increase in paradoxical sleep duration, whereas it caused a decrease when injected during the dark period. Anti-prolactin antibody injection during the dark period also decreased paradoxical sleep duration. There was no effect of oPRL or antibody on slow wave sleep duration irrespective of injection time. These results suggest that prolactin injection may have an inhibitory effect on hypothalamic prolactin neurons.

Animals↗

Promotion of sleep by prostaglandin D2 in rats made insomniac by pretreatment with para-chlorophenylalanine.

The correlation between the somnogenic effect of prostaglandin (PG) D2 and the serotoninergic system was examined in freely-moving rats (n = 64) by use of a continuous infusion method. Rats pretreated with para-chlorophenylalanine (PCPA: 450 mg/kg body weight, i.p.) or non-PCPA-pretreated rats received infusion of PGD2, serotonin, or its direct precursor, 5-hydroxytryptophan (5HTP), into their third cerebral ventricle at a rate of 100 pmol/0.2 microliter/min between 11:00 and 17:00 h. In the PCPA-pretreated insomniac rats, PGD2 infusion resulted in an immediate increase in slow-wave sleep (SWS) and an increase with a 2-h latency in paradoxical sleep (PS). The total amounts of SWS and PS during the PGD2-infusion period were 151% and 154% of the respective control values. These results indicate that inhibition of the biosynthesis of serotonin and 5HTP by PCPA marginally affects the sleep-promoting effect of PGD2. The transient sleep restoration produced by 5HTP infusion into PCPA-pretreated rats was hardly affected by the simultaneous infusion (200 pmol/0.2 microliter/min; 07:00-17:00 h) of diclofenac sodium, an inhibitor of cyclo-oxygenase, suggesting that PGD2 production is not critically involved in the sleep restoration by 5HTP. The sleep-promoting property of PGD2 is thus probably independent of the serotoninergic modulation of sleep-wake activity.

5-Hydroxytryptophan↗

Glutamine synthetase modulation in the brain of rats subjected to deprivation of paradoxical sleep.

Changes in the level of glutamine synthetase (GS), an enzyme mainly located in astrocytes, were investigated in rat brain after deprivation of paradoxical sleep (PSD) and during recovery. An immunotitration method was used to evaluate the relative level of GS in brain tissue. At the end of a 24 h PSD, a significant increase in GS protein was observed both in the frontoparietal cortex (CX) and in the locus coeruleus area (LC). Four hours later during recovery, the level of GS protein returned to normal level in the CX but fell below control levels in the LC. In contrast, in the CX, the level of glial fibrillary acidic protein, an astroglial marker, did not change after PSD or during recovery. GS mRNA was quantified in the entire cortex by northern blot hybridization using of an oligonucleotidic GS-cDNA probe. We observed an increase in the GS mRNA level in the cortex of PSD rats of the same magnitude as the increase in GS protein. Both GS mRNA and GS protein tended to return to control values 4 h later during recovery. These results are discussed with particular attention to stress effects and possible physiological mechanisms regarding the regulation of amino acid levels by neurotransmitters during prolonged waking or neuronal excitation.

Animals↗

Effects of modafinil-induced wakefulness on glutamine synthetase regulation in the rat brain.

Changes in the level of glutamine synthetase (GS), an enzyme chiefly found in glial cells, were investigated in the brains of rats treated with modafinil, an awakening drug interfering with central catecholamine function. Two hours (waking period) and 7 h (recovery period) after intra-peritoneal injection of 128 mg/kg modafinil, a significant increase in the level of GS protein was observed by immunotitration in both the locus coeruleus (+30%) and in the frontoparietal cortex (+50%). No changes were observed with 64 mg/kg of modafinil. GS mRNA was quantified in the entire cortex by Northern blot hybridization using an oligonucleotidic GS cDNA probe. A significant increase in the GS-mRNA level (+70%) was observed in the CX of rats 2 h after injection of 128 mg/kg modafinil; the level tended to return to control values 7 h later during the recovery period. The level of glial acid fibrillary protein (GFAP), an astroglial marker, was unchanged after modafinil treatment. These changes in GS levels after modafinil treatment are discussed in terms of neuron-glia interactions in the regulation of brain metabolism during pharmacologically induced wakefulness, excluding possible stress effects.

Animals↗

VIP binding sites in adult rat hypothalamus: nuclear distribution and daily variations.

Vasoactive intestinal peptide (VIP) neurons are present in the suprachiasmatic nucleus (SCN) and project to various hypothalamic nuclei. Several results suggest that hypothalamic VIP is involved in the mediation of synchronizing information. [125I]Vasoactive intestinal peptide binding has been reported to be especially high in the hypothalamus. We show here by radioautography by dipping that [125I]VIP binding is high and homogeneously distributed in the SCN. The correspondence between VIP binding and terminals densities supports the hypothesis that VIP acts through synapses in the SCN. Moderate and fairly homogeneous VIP binding is also found in the paraventricular nucleus (PaVN), whereas VIP terminals are reported to be restricted to the sub-paraventricular area. This suggests that VIP could diffuse and thus function as a paracrine neuromodulator in the PaVN. [125I]Vasoactive intestinal peptide binding is stable along the nycthemer in the suprachiasmatic, peri-, and paraventricular nuclei as well as in all other areas investigated.

Animals↗

Monoamine oxidase: distribution in the cat brain studied by enzyme- and immunohistochemistry: recent progress.

Localization of MAO-containing neurons, fibers and glial cells has been described by recent progress in MAO histochemistry and immunohistochemistry. It does not necessarily correspond to those containing monoamines. MAO-A is demonstrated in many noradrenergic cells, but it is hardly detectable in DA cells. Increase of 5-HT and DA concentration after inhibition of MAO-A indicates the possible existence of MAO-A in such neuronal structures. MAO-A is also undetectable in neurons containing 5-HT, a good substrate for MAO-A. These neurons contain MAO-B. There still remain contradictions to be solved in future. MAO is present in astroglial cells, in which monoamines released in extracellular space may be degraded. In glial cells, MAO may also play a role to regulate concentration of telemethylhistamine and trace amines. Such cells appear to transform MPTP to MPP+, a neurotoxin for nigral DA neurons.

Animals↗

Quantitative and qualitative aspects on the distribution of 5-HT and its coexistence with substance P and TRH in cat ventral medullary neurons.

By use of the indirect immunofluorescence technique the distributions of 5-hydroxytryptamine (5-HT)-, substance P- and thyrotropin-releasing hormone (TRH)-immunoreactive (IR) neurons have been studied in the midline raphe nuclei and nucleus reticularis lateralis of the caudal brainstem (levels P18.3-P8.5; according to Berman (1968), in the cat, after treatment with colchicine. In addition, by use of the double-labelling technique, the coexistence between 5-HT-, substance P- and TRH-like immunoreactivity (LI) in these neurons was analysed. The results show that cell bodies in the midline raphe nuclei and nucleus reticularis lateralis contain 5-HT-, substance P- and TRH-LI. 5-HT-IR cells were more abundant than peptidergic neurons in all areas analysed. Quantitative estimations indicated that the total number of 5-HT-IR cells in the regions studied was about 17 x 10(3), while the corresponding numbers for substance P- and TRH-IR cells were 11 x 10(3) and 12 x 10(3), respectively. From double-labelled sections it was concluded that the vast majority of peptidergic cells also contained 5-HT-LI (87-100%). However, a subpopulation of 5-HT-IR neurons lacked peptide-LI (10-55%). The degree of coexistence varied with the brainstem level, in that neurons at more rostral locations showed a lower incidence of coexistence between 5-HT and peptide(s). The presence of all three compounds in one and the same cell body could also be demonstrated. In summary, 5-HT-, substance P- and TRH-IR cell bodies were encountered in medullary nuclei known to contain neurons with projection to the spinal cord. A high degree of coexistence between the compounds was demonstrated in these nuclei. The obtained results fit well with earlier studies on the patterns of distribution and peptide colocalization of 5-HT fibres in the spinal cord. The existence of biochemically distinct neuronal subpopulations within the 5-HT bulbospinal pathway is discussed.

Animals↗

Paradoxical sleep mechanisms.

A review of the effects of brain-stem transections, carbachol microinjections and lesions does not show that the pons is necessary and sufficient for paradoxical sleep (PS) generation. The different theories that explain the mechanisms of PS rebound are summarized. In some circumstances, PS rebound depends upon the stressful quality of PS deprivation. PS appears to necessitate oxidative metabolism of glucose and, in certain situations, PS may be increased by hyperoxia.

Brain Stem↗

Thermal diffusion probe and instrument system for tissue blood flow measurements: validation in phantoms and in vivo organs.

A minimally invasive probe and instrument system for real-time measurements of temperature, thermal conductivity and tissue blood flow has been designed for research and clinical use. The essence of the probe is a thermistor, located at the tip of catheters or glass and steel needles, and operating in transient self-heated mode at constant temperature increment. Thermal conductivity and tissue blood flow are determined by use of a coupled tissue-probe thermal model. The effects of temporal baseline temperature shifts are minimized by a novel, automatic, analog compensation circuit. Very short heating periods (3 s) and cooling periods (12 s) provided near-continuous measurements (4/min). Calibration experiments performed in media of known thermal conductivity exhibit a linear response with respect to thermal conductivity. In vitro experiments performed in isolated perfused dog liver preparations are presented to evaluate this instrument system. In vivo experiments performed in cat brain, dog liver, and human tumor demonstrate the ability of this instrument system to perform physiologically valid measurements (comparison inter-subjects and intra-subjects). The minimally invasive probes (0.8 mm OD) are capable of long term measurements (several months), with minimal tissue reactions (0.3 mm around the probe).

Animals↗

Power spectral analysis of blood pressure fluctuations during sleep in normal and decerebrate cats.

Arterial blood pressure fluctuations during sleep were investigated with power analysis technique in both normal and decerebrate cats. In the initial postoperative stage lasting about 3 to 4 days, intact cats displayed, during paradoxical sleep, phasic increases in arterial blood pressure which were superimposed on a tonic hypotension. In the later chronic stage, however, the animals showed the phasic hypertension being superimposed on the background of a tonic hypertension. Regardless of these stages, the blood pressure during paradoxical sleep exhibited a 1/f-like spectrum, expressed by the power spectral density which is inversely proportional to the Fourier frequency f. On the other hand, a power spectral profile of the blood pressure during slow wave sleep presented a white noise-like pattern within the same frequency range of 0.1-0.01 Hz. After brainstem transections at the pontomesencephalic border, the cats exhibited consistently a sustained fall in blood pressure during paradoxical sleep and the power spectral density of the blood pressure displayed a white noise-like pattern throughout the survival periods of one month or more. These observations indicate that the blood pressure fluctuations in the 1/f spectrum during paradoxical sleep originate in rostral brain structures.

Animals↗

[Phylogeny of sleep stages].

The states of sleep in man (orthodox and paradoxical sleep) are the achievement of a long evolution which has successively integrated several mechanisms. The circadian clock (predictive homeostasis) a system responsible for saving energy utilisation, a mechanism which adapts the duration of sleep to the preceding duration of waking (reactive homeostasis) and finally the apparition of an ultradian pace maker in homeothermic mammals which will be responsible for dreaming in man.

Adult↗

Effect of prolactin on the sleep-wake cycle in the rat.

The purpose of this study was to examine the effects of prolactin on the sleep-wake cycle. Ovine prolactin was injected subcutaneous at a dose of 10 micrograms/animal or intra-cerebro-ventricularly at doses of 100, 10 and 1 ng/animal. The subcutaneous injections were given during either the diurnal or nocturnal period. Results indicate that oPRL decreases paradoxical sleep duration when injected during the dark period and increases it when injected during the light period. The i.c.v. injections were given only during the dark period and the effects were similar to those obtained with the s.c. injections. There was no effect on slow-wave sleep duration irrespective of injection time or injection site.

Activity Cycles↗

Spectral analyses of PGO-on neurons during paradoxical sleep in freely moving cats.

We have investigated the power spectral density (PSD) characteristics of spontaneous neuronal activities during paradoxical sleep (PS), including phasically firing PGO-on and tonically discharging type I-R neurons in the pontine tegmentum. The PSD of lateral geniculate PGO waves and blood pressure (BP) were also examined. During PS, the PSD of PGO-on neurons and PGO waves showed an almost white noise-like pattern, while that of TI-R neurons and BP exhibited a 1/f spectrum. It appears, therefore, that the neuronal and autonomic slow fluctuations found in the 1/f spectrum during PS are not driven by the PGO wave system.

Animals↗

Histaminergic system in the cat hypothalamus with reference to type B monoamine oxidase.

It is known that histamine (HA) and type B monoamine oxidase (MAO-B), an enzyme involved in its metabolism, are present in the posterior hypothalamus, but the sites where MAO-B intervenes in HA metabolism remain uncertain. The present study examined and compared the detailed distribution and morphology of neurons immunoreactive to HA (HA-ir) and MAO-B (MAO-B-ir) in the cat hypothalamus. HA-ir neurons were localized almost exclusively in the posterior hypothalamus with the largest group in the tuberomammillary nucleus and adjacent areas. MAO-B-ir staining was detected in the vast majority of HA-ir neurons, suggesting that the degradation of tele-methylhistamine (t-MHA), the direct metabolite of HA, may occur within these cells. Nevertheless, a few HA-ir cells showed no detectable or very weak MAO-B-ir labeling; a small group of neurons containing MAO-B alone was detected in the area dorsolateral to the caudal part of the arcuate nucleus. Numerous HA-ir axons and terminal-like structures were distributed unevenly in virtually all hypothalamic regions. One of their principal trajectories ascended through the ventrolateral part of the hypothalamus and rostrally formed an axon column, which ascended into the preoptic area and contributed fibers to the diagonal band of Broca and bed nucleus of the stria terminalis. Other HA-ir axons passed laterally, dorsal to the zona incerta or ventrally through a narrow zone dorsal to the optic tract. Numerous long HA-ir axons coursed dorsomedially from the ventrolateral posterior hypothalamus to the dorsal hypothalamic area. Many are oriented vertically to the thalamus in the midline. MAO-B-ir axons and fibers were detectable throughout the hypothalamus and overlapped the areas distributing HA-ir fibers. They were, however, weaker in staining intensity and apparently fewer than the HA-ir fibers. MAO-B-ir glial cells were numerous in all hypothalamic structures rich in HA-ir fibers. These results suggest that the metabolism of t-MHA may also occur within HA terminals and glial cells.

Animals↗

Daily variations in concentration of vasoactive intestinal peptide immunoreactivity in hypothalamic nuclei of rats rendered diurnal by restricted-schedule feeding.

We previously described that in the suprachiasmatic (SCN), peri-(PeVN) and paraventricular (PaVN) nuclei of normal rats, vasoactive intestinal peptide (VIP)-like immunoreactivity (VIP-LI) accumulates during the night period and decreases during the day. In order to determine whether these variations are linked to the light-dark cycle or are a consequence of sleep-wake rhythm expression, we dissociated these two parameters by restricting feeding to diurnal hours. In these conditions which inverse the paradoxical sleep rhythm, the VIP-LI pattern is perturbed and its minimum advanced by 4 h in the SCN. In the PeVN, the daily pattern is maintained but the minimum is also advanced by 4 h. Finally, the rhythm is abolished in the PaVN. These circadian fluctuations indicate that the hypothalamic VIP-LI rhythm is not linked to the paradoxical sleep rhythm but could be sensitive to photic and non-photic Zeitgeber.

Animals↗

Daily variations in in vivo tryptophan hydroxylation and in the contents of serotonin and 5-hydroxyindoleacetic acid in discrete brain areas of the rat.

The in vivo rate of brain tryptophan hydroxylation was determined through 5-hydroxytryptophan accumulation (5-HTPacc) following the administration of NSD 1015, a L-aromatic amino-acid decarboxylase inhibitor. This measurement was performed every 4 h throughout a 24 h hour period in 10 discrete brain areas of rats maintained on a regular 12 h/12 h light-dark cycle. The concentrations of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were also determined in untreated rats. Daily variations in 5-HTPacc were found in all the areas studied, the 5-HTPacc being higher during the dark period in most structures. These results strongly suggest that tryptophan hydroxylation is involved in the control of the 5-HT biosynthesis circadian rhythm. However, various patterns of 5-HT and 5-HIAA daily variations were observed, suggesting that the circadian factors affecting serotonin metabolism can be different among brain areas.

5-Hydroxytryptophan↗

Chromatographic analysis of the enkephalin immunoreactivity in the nucleus locus coeruleus of the cat after local colchicine administration.

Cell bodies immunoreactive for methionine- and leucine-enkephalin are found in the area of the locus coeruleus (dorsolateral pons) of the cat after injection of colchicine in the ascending projections of the nucleus. Using radioimmunoassay procedures, it is shown that colchicine induces a significant increase in methionine- and leucine-enkephalin-immunoreactive material in this area of the brain. High pressure liquid chromatography analysis demonstrated that the immunoreactive materials were authentic methionine- and leucine-enkephalin. The methionine- and leucine-enkephalin patterns were identical in the colchicine injected and non-injected sides of the dorsolateral pons. It is suggested that, in this area of the brain, colchicine (i) does not significantly modify the processing of proenkephalin to form the pentapeptides methionine- and leucine-enkephalin, and (ii) does not induce the appearance of new substances reactive to the enkephalin antisera employed.

Animals↗

[Sleepiness. Experimental models].

Some experimental models of sleepiness are reviewed. The model of the narcoleptic dog is the best one to study the mechanisms of cataplexy. Idiopathic sleepiness can be experimentally studied by acting upon either circadian or homeostatic regulation of sleep. The paradoxical sleep rebound which occurs after its previous suppression has been explained by different theories which are summarized. Finally, the decrease of waking which follows either lesion or pharmacological alterations is useful to develop new molecules which can increase waking, in a safe manner.

Animals↗