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Biomedical subjects

P Bobillier

Publications and source records attributed to P Bobillier.

At least 37 records · Page 2Linked to original sources
PubMed1991

Decreased protein synthesis in hypothalamic nuclei following L-5-hydroxytryptophan in intact and p-chlorophenylalanine-pretreated rats.

The rate of protein synthesis was estimated in individual hypothalamic nuclei by a quantitative autoradiographic technique with L-[35S]methionine. The i.v. administration of 60 mg/kg L-5-hydroxytryptophan (40 min before) resulted in a 45-55% decrease of overall protein synthesis rate in all the hypothalamic nuclei examined. In rats pretreated (42 h before) with a single i.v. injection of 280 mg/kg p-chlorophenylalanine, a drug which is known to deplete brain serotonin concentration, the administration of 60 mg/kg L-5-hydroxytryptophan resulted in a 50-75% decrease of protein synthesis rates in the hypothalamic nuclei. These results suggest that the systemic administration of large doses of L-5-hydroxytryptophan may inhibit protein synthesis in hypothalamic nuclei directly or indirectly after the conversion of this compound to serotonin.

5-Hydroxytryptophan↗
PubMed1991

[Brain protein synthesis in awake rats: equilibrium of L-methionine between plasma and direct precursor pool].

After 1 hr. of continuous infusion of L-(35S)methionine the specific activities of L-methionine in plasma and tissue-free and tRNA-bound L-methionine in brain were in the same range. This result indicates that, under steady-state conditions, dilution of the precursor pool for protein synthesis (L-methionyl-tRNA) by L-methionine derived from a source other than plasma can be considered as negligible.

Animals↗
PubMed1990

Restraint stress and adrenalectomy do not affect the level of rat cerebral enolase.

Gamma gamma (gamma gamma) enolase amount and enolase isozyme activities were measured in brain structures involved in stress response (hypothalamic paraventricular and supraoptic nuclei, locus coeruleus, hippocampus, A1 and A2 regions, hypophysis). Analyses were made in rats after immobilization or adrenalectomy, two experimental conditions that have been reported to increase brain glucose consumption and protein synthesis. In control rats enolase content was highest in the A1 region and hippocampus and lowest in hypophysis. A positive correlation was found between the enzyme level and its activity in the brain regions studied. However, in stressed or adrenalectomized rats, the level of glycolytic enzyme enolase was not significantly modified.

Adrenalectomy↗
PubMed1990

Neurons containing messenger RNA encoding glutamate decarboxylase in rat hypothalamus demonstrated by in situ hybridization, with special emphasis on cell groups in medial preoptic area, anterior hypothalamic area and dorsomedial hypothalamic nucleus.

Previous deafferentation studies have suggested that most hypothalamic GABAergic innervation originates from neurons within the hypothalamus. We have investigated the distribution of GABAergic cell groups in the rat hypothalamus by means of the in situ hybridization technique, using a cDNA probe for messenger RNA encoding glutamate decarboxylase. Several major GABAergic cell groups were demonstrated, including cells of the tuberomammillary nucleus, arcuate nucleus, suprachiasmatic nucleus, medial preoptic area, anterior hypothalamic area, the dorsomedial hypothalamic nucleus, perifornical area, and lateral hypothalamic area. The most prominent glutamate decarboxylase mRNA-containing cell groups were located in the medial preoptic area, anterior hypothalamic area and dorsomedial hypothalamic nucleus, and were composed of small- to medium-sized neurons. Compared to previously well-characterized GABAergic cell groups in the tuberomammillary nucleus, reticular thalamic nucleus, and non-pyramidal cells of cerebral cortex, the cells of these GABAergic groups demonstrated only weak cDNA labelling, indicating that they contain lower levels of glutamate decarboxylase mRNA. Several types of control experiments supported the specificity of this cDNA labelling, and the GABAergic nature of these cell populations was further supported by detection of glutamate decarboxylase and GABA immunoreactivity. Abundance of GABAergic cells in many hypothalamic nuclei indicates that GABA represents quantitatively the most important transmitter of hypothalamic neurons, and may be involved in neuroendocrine and autonomic regulatory functions.

Animals↗
PubMed1989

Demonstration of GABAergic cell bodies in the suprachiasmatic nucleus: in situ hybridization of glutamic acid decarboxylase (GAD) mRNA and immunocytochemistry of GAD and GABA.

The existence of GABAergic neurons in the rat suprachiasmatic nucleus (SCN) was demonstrated by three specific markers; mRNA coding for glutamic acid decarboxylase (GAD) and visualized by in situ hybridization using a 35S-labelled cDNA probe, and GAD protein and GABA were identified by immunocytochemistry using specific antisera. In situ hybridization demonstrated well labelled GAD mRNA positive cells throughout SCN, and GABA and GAD immunoreactive cells showed similar distributions. These results indicate that GABA is a transmitter of a large portion of the SCN neuronal population.

Animals↗
PubMed1989

The effects of melatonin and pinealectomy upon local cerebral glucose utilization in awake unrestrained rats are restricted to a few specific regions.

The effects of the infusion of melatonin (MT) and/or of pinealectomy upon glucose utilization in anatomically discrete regions of the brain of freely moving rats have been studied by the quantitative autoradiographic 2-deoxy-D-[1-14C]glucose technique. The experiments were made from 14.00 to 16.00 h, when MT is normally not secreted by the pineal gland, in order to compare the local cerebral glucose utilization (LCGU) response to MT from animals with long-term (pinealectomized) or short-term (pineal intact) absence of MT secretion. The majority of the 98 brain areas examined showed no change in LCGU after MT administration and/or pinealectomy. Pinealectomy increased the LCGU in the median mammillary nucleus only, whereas following MT administration, an increase in LCGU was observed in 3 cerebral regions of intact rats (paraventricular nucleus of the hypothalamus, nucleus of the solitary tract, choroid plexus of the third ventricle) and in 5 cerebral regions of pinealectomized rats (paraventricular nucleus of the hypothalamus, nucleus of the solitary tract, choroid plexuses of the lateral ventricles, third and fourth ventricles). Except for the choroid plexuses of the fourth ventricle, there was no difference in LCGU response to MT between pinealectomized and intact animals. This does not favor the hypothesis of receptor supersensitivity under the conditions of this experiment. Our results suggest that the hypothalamus, nucleus of the solitary tract and choroid plexuses represent a neural substrate through which MT could influence the activity of the central nervous system when administered at a low dose under near-physiological conditions.

Animals↗
PubMed1989

Apomorphine-induced inhibition of substantia nigra dopamine neurons: effects of unilateral injection through the internal carotid artery.

Possible indirect components in the inhibition of firing of A9 dopamine neurons induced by systemic apomorphine were studied using unilateral drug administration through the internal carotid artery, known to irrigate only the ipsilateral mid- and forebrain. When compared to intravenous injection, unilateral intracarotid administration inhibited ipsilateral neurons with a marked decrease of both the latency (less than 1 s) and the dose required for complete inhibition, whereas contralateral neurons were not affected. This suggests a first-pass central effect of apomorphine, presumably associated with brain extraction. Thus, peripheral and hindbrain targets do not seem to contribute to the inhibitory effect of low doses of systemic apomorphine. An intranigral possible mode of action is discussed in view of the particular arrangement of dopaminergic dendrites within the zona reticulata.

Action Potentials↗
PubMed1989

RU 24722, a new eburnamine derivative, induces selective alterations in cerebral glucose utilization in freely moving rat.

The effect of a new eburnamine derivative, RU 24722, a putative phasic activator of catecholaminergic systems on local cerebral glucose utilization was studied in freely moving rats 15 min, 90 min and 6 h after the intraperitoneal administration of the drug (25 mg/kg). Of the 53 brain regions examined, 9 exhibited significant time-dependent increases of glucose utilization (up to 45-55%). Some changes were early and transient, as in the substantia nigra reticulata and the paraventricular nuclei. Other areas showed sustained (median septal nucleus) or delayed increases of glucose utilization (lateral septum, dorsal subiculum, hippocampal fimbria, fronto-parietal motor cortex and ventral cochlear nucleus). No significant alterations of glucose utilization could be elicited in the locus coeruleus and raphe nuclei, and none of the brain regions showed a decrease in glucose consumption. Our findings suggest that RU 24722 preferentially stimulates the activity in some brain areas involved in cognitive, vegetative and locomotor functions.

Animals↗
PubMed1988

Plasma, cerebrospinal fluid, and brain distribution of 14C-melatonin in rat: a biochemical and autoradiographic study.

The distribution of 14C-Melatonin (14C-MT) after systemic injection was studied in the plasma, cerebrospinal fluid (CSF), and brain of rats. Chromatographic analysis (thin-layer chromatography and high-performance liquid chromatography) indicated that the radioactivity from biological samples taken at various times following the injection of label was mainly associated with 14C-MT. Computer analysis of plasma 14C-MT kinetics showed a three-compartment system with half-lives of 0.21 +/- 0.05, 5.97 +/- 1.11, and 47.52 +/- 8.86 min. The volume of distribution and the clearance were 1,736 +/- 349 ml.kg-1 and 25.1 +/- 1.7 ml.min-1.kg-1 respectively. The entry of 14C-MT into the CSF was rapid and reached a maximum at 5 min. The decay followed a two-compartment system with half-lives of 16.5 +/- 2.9 and 47.3 +/- 8.6 min. The CSF/plasma concentration ratio was 0.38 at the steady state (30 min). At 2 min the level of 14C-MT in the brain was 3.8 higher than in the CSF. Representative autoradiograms revealed an heterogeneous localization of 14C-MT in the grey matter. The highest regional values, as evaluated by the permeability area product technique, were found in cortex, thalamic nuclei, medial geniculate nucleus, anterior pretectal area, paraventricular nucleus of the hypothalamus, choroid plexuses, and bulb-pons. Thirty minutes later 14C-MT was still detected in most of the brain regions analyzed. These results point to a low but rapid penetration of circulating MT into the brain and the CSF. The heterogeneous distribution and the partial retention of 14C-MT in the brain are compatible with the hypothesis of a central action of this hormone mediated via binding sites.

Animals↗
PubMed1988

Localization of cerebral protein synthesis alterations in response to water deprivation in rats.

The effects of 2 days of water deprivation on local rates of methionine incorporation into protein in 54 brain and 5 circumventricular structures of conscious freely moving rats have been examined by means of a recently developed quantitative autoradiographic method with L-[35S]-methionine. The results show that 2 days of water deprivation does not affect methionine metabolism in the majority of the brain areas analyzed, but reveals selective increases in the hypothalamoneurohypophyseal system, in cerebral structures surrounding the third ventricle, in the locus ceruleus, raphe dorsalis, nucleus ambiguus and hippocampal CA3 layer. In contrast, decreases were observed in the central amygdala, lateral habenula and interpeduncular nucleus. Although the highest increases were located in brain areas involved in body fluid homeostasis, several aspecific responses, perhaps due to chronic stress, were also observed, notably in the locus ceruleus, raphe dorsalis and in a restricted number of limbic system structures.

Animals↗
PubMed1987

An in vivo kinetic model with L-[35S]methionine for the determination of local cerebral rates for methionine incorporation into protein in the rat.

A method has been developed for the simultaneous in vivo measurement of local rates for methionine incorporation into cerebral protein in the rat. It is based on the use of L-[35S]methionine as a tracer for reflecting the bidirectional exchange of methionine between plasma and brain and its incorporation into cerebral protein, using a dynamic three-compartment model. An operational equation based on this model has been derived in terms of determinable variables. The method has been applied to the normal freely moving rat and to the rat under chloral hydrate anesthesia. In the freely moving rat, the values of methionine incorporation into cerebral protein in the gray matter vary widely from structure to structure (50-300 nmol/100 g/min), with the highest values in structures related to neurosecretory functions, e.g., supraoptic and paraventricular nuclei. The values for white matter are more uniform (24-28 nmol/100 g/min) at levels approximately six- to seven-fold lower than for gray matter. Chloral hydrate anesthesia depresses the rate of methionine incorporation in all the structures examined. Anesthesia did not reduce the heterogeneity normally present within gray matter.

Animals↗
PubMed1986

Stress and local cerebral blood flow: studies on restrained and unrestrained rats.

The degree of stress has been compared between two protocols used for the measurement of local cerebral blood flow (LCBF) in conscious rats. The first method involved acute surgical procedures (cannulation of both femoral veins and arteries) under halothane anesthesia. It was followed by a recovery period (2-3 h) during which the rat was before LCBF measurement. The second method employed chronic cannulation of the abdominal aorta and vena cava, allowing the LCBF assays to be performed on freely moving rats. Plasma corticosterone and a glucose tolerance tests showed that the freely moving rats were less stressed than the gently restrained ones. The LCBF of the two groups were not significantly different except in the frontal and parietal cortex, where it was more elevated in the freely moving rats. LCBF may be sensitive to the environmental conditions in freely moving rats whereas these vascular effects may be reduced after 2-3 h of gentle restraint. The two protocols tested in this study could be considered as good methods for studying LCBF in conscious rats, although some stress remained in gently restrained rats. Freely moving rats can be used for behavioural studies providing that the time lag of the arterial samples is taken into account. Since the basal LCBF values of gently restrained rats are minimally affected by the stress inherent in the preparation, this convenient protocol could be considered as useful for numerous investigations.

Animals↗
PubMed1986

[Effects of acute or chronic administration of desmethylimipramine on the local level of methionine incorporation in cerebral proteins in freely moving rats].

Incorporation of methionine into brain proteins has been measured by quantitative autoradiography after desmethylimipramine administration in rats. Acute treatment decreased protein synthesis in three regions: hippocampus, hypothalamus and habenula. After chronic treatment the decrease extended to four other regions: substantia nigra, raphe dorsalis, trigeminal nerve and hypophysis. An opposite effect was observed in the retrosplenial cortex.

Animals↗
PubMed1985

Differential effects of chronic dehydration on protein synthesis in neurons of the rat hypothalamus.

The rate of methionine incorporation was measured in individual hypothalamic nuclei by a quantitative autoradiographic technique: the L-[35S]methionine method. Physiological stimulation of the hypothalamo-neurohypophysial system by two days of water deprivation, a stress that increased the plasma total neurophysins concentration 4-5-fold, resulted in a 70-80% increase in overall protein synthesis in the supraoptic nucleus and in the magnocellular subdivisions of the paraventricular nucleus. The same stimulus had no effect on protein synthesis rate of the suprachiasmatic nucleus and of the other representative cerebral structures examined. This differential effect on protein synthesis was also observed within the paraventricular nucleus.

Animals↗
PubMed1985

Autoradiographic and quantitative study of benzodiazepine-binding sites in human hippocampus.

Benzodiazepine-binding sites were studied on frozen sections of 5 human hippocampi, using autoradiographic and biochemical techniques. The affinity, density, distribution and heterogeneity (two types) of sites were investigated using [3H]flunitrazepam as a ligand, clonazepam or C1 218872 as displacing agents. The autoradiographic images evidence a differential distribution of the binding sites in the histologic layers of the hippocampus. Subtypes I and II coexist in the same proportion in the three layers exhibiting the highest densities of binding sites (stratum granulosum and pyramidale, deep layer of stratum radiatum). The Kd, Bmax and Ki values found here are analogous to those described in animal studies, but the anatomical distribution of the sites in human hippocampus seems to differ slightly from that previously described in that of the rat.

Adolescent↗
PubMed1985

A chronic arterial and venous cannulation method for freely moving rats.

A chronic arterial and venous cannulation method appropriate for pharmacokinetics studies in freely moving rats is described. Two catheters were implanted: one in the abdominal aorta, the other in the inferior vena cava. Passing subcutaneously, the catheters then emerged at the nape of the neck and were sealed by heating. In most cases (70%), 2-3 weeks after surgery, there were no problems of catheter patency. Twenty-four hours after surgery, all the animals were in good health as attested by normal behaviour and physiological parameters. Plasma corticosterone levels (544 +/- 219 ng/ml) determined at various times after an i.v. injection of saline, though 2.4-fold lower than in restrained rats (1330 +/- 292 ng/ml), were, however, indicative of a moderate stress. From a differential analysis of the factors involved in the relatively elevated circulating corticosterone as compared to basal levels, it is concluded that a prolonged postoperative period (7 days) and maintaining of the animals in metabolic cages are necessary conditions to obtain a minimal state of stress with this technique.

Anesthesia, General↗
PubMed1984

Autoradiographic localization of [14C]8-S-adenosyl-L-homocysteine in rat brain.

Following intracarotid injection of [14C]8-S-adenosyl-L-homocysteine ( [14C]SAH) in the rat, radioactivity was localized by autoradiographic detection in the circumventricular organs, such as the pineal gland, choroid plexuses and area postrema, which lie outside the blood-brain barrier. HPLC analysis indicated a decrease of [14C]SAH radioactivity in these structures from 1 to 45 min, after injection. These results are discussed and related to the known pharmacological properties of SAH.

Animals↗