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S Nicolaidis

Publications and source records attributed to S Nicolaidis.

At least 73 records · Page 4Linked to original sources

Physiological determinant of hunger, satiation, and satiety.

The initiation and cessation of feeding behavior is explained on the basis of the ischymetric hypothesis (from ISCHYROS meaning "Mighty One" or power). Cellular production of power or "Metabolisme de Fond" (MF) is measured continuously in terms of total body metabolism minus the metabolic costs of locomotion. A drop in MF signals the onset of eating. Eating initiates a rise in MF and when this signal peaks, the feeding process stops. Control of satiation is described in terms of recent neurophysiologic and neuroendrologic factors that influence MF.

Animals↗

Chronic intracerebroventricular infusion of insulin causes selective increase of slow wave sleep in rats.

Sleep patterns were continuously recorded in rats receiving chronic intracerebroventricular (i.c.v.) infusions of insulin. The i.c.v. administration of insulin resulted in a selective increase (25%) of the daily duration of slow wave sleep (SWS), whereas the duration of paradoxical sleep (PS) remained unchanged. The neutralization of peripheral and/or central insulin by means of continuous intravenous or i.c.v. infusions of anti-insulin serum brought about a selective decrease of SWS, whereas PS remained unchanged. The present findings are discussed with regard to the present knowledge of the origin and the role of brain insulin.

Animals↗

Electrophysiological investigation of cells in the region of the anterior hypothalamus firing in relation to blood pressure and volaemic changes.

The anterior hypothalamus has been implicated in the higher centre control of blood pressure and more recently in hydromineral balance regulation. Using a glass recording electrode with and without a 7-barrelled iontophoretic electrode we investigated this region for blood pressure-sensitive cells. We used a ventral approach through the optic chiasma. We found 36 cells out of 91 tested that increased their firing rate in response to a spontaneous or induced decrease in blood pressure. Of these 19 increased firing in response to angiotensin II (AII) injected into the lateral cerebral ventricle and 10 of these increased firing in response to local iontophoretic application of AII. Cells responsive to an increase in blood pressure were never found. Thus cells in this area respond to hypovolaemia and hypotension as well as to AII, which could link this area with higher centre responsiveness to stimuli of extracellular thirst.

Angiotensin II↗

Converging projections of hydromineral imbalances and hormonal co-action upon neurons surrounding the anterior wall of the third ventricle.

Various structures have been found in the anterior third periventricular area (A3pV) which seem to be concerned with hydromineral imbalances, since they contain neurons which can sense changes in osmolality, blood volume, blood pressure, angiotensin II [Ang II] levels and temperature. These neurons also seem to be concerned with the setting in action of corrective responses at an autonomic or behavioural level. The discovery of neurons in this area that respond to more than one signal (for example osmotic and volaemic, or blood pressure and Ang II levels) suggested that this area has an integrative role. More recent findings from stimulation and lesion experiments have shown that the broadly inter-connected A3pV structures which extend from the region of the suprachiasmatic nucleus to the subfornical organ (SFO), are targets for many stimuli. Our recent electrophysiological data have strengthened the idea of an integrative role for A3pV structures. Iontophoretic application of various substances has shown that a single baro-sensitive neuron can have its firing modulated by Ang II. In the present paper we report the discovery of A3pV neurons which respond to both Ang II and vasopressin (VP). Furthermore the co-action of these two hormones may be subtractive, additive or even potentiating depending on conditions. It appears that, in addition to detecting hydromineral imbalances, the A3pV neurons can sense the presence of at least two sister hormones which can co-modulate their responsiveness.

Angiotensin II↗

[Basal metabolism: definition and apparatus for its measurement].

The " Metabolisme de Fond" (MF) is defined as the energy expenditure of the whole body cells, except for the energy devoted to the locomotor activity. The continuous measurement of the MF is performed in the free moving rat using a computer-controlled open circuitry calorimeter. This system provides simultaneous measurement of the metabolic parameters (oxygen, carbon-dioxide, respiratory quotient) as well as the quantification of the behavioral parameters (food intake, locomotor activity, sleep). The measurement of the MF is based on the calculation of the slope of the curve linking the relative changes in the intensity of respectively locomotor activity and total metabolism. Such a computation of the MF requires the precise analysis and the subsequent mathematical correction of the physical phenomena occurring in an open circuitry calorimeter. Indeed the instantaneous electrical signal of locomotor activity is recorded before the delayed and distorted corresponding increase in the energetic metabolism which must be corrected. In conclusion, the method described here allows the direct determination of quick MF modifications in the freely behaving rat.

Animals↗

[Measurement of basal metabolism in relation to food intake : ischymetric hypothesis].

The ischymetric hypothesis of the control of food intake ( ischys = power in greek) suggests that the physiological stimulus of hunger is characterized by the decrease of the "m etabolisme de fond". In the same way, satiety would occur as long as the MF remains at a high level. The complex problems dealing with the continuous measurement of the MF in the free behaving Rat have been solved recently. As a consequence, it has been possible to test directly the ischymetric hypothesis by measuring the MF oscillations around six meals taken by the same Rat during a 24 hrs. experiment. The results showed that the meals are indeed preceded by a progressive decrease of MF and that the termination of meals coincides with a high metabolic rate. The rapid increase of the MF occurring immediately after the onset of the meals could reflect the oropancreatic reflex inducing the well known anticipatory release and utilization of the endogenous reserves. If anything, the respiratory quotient exhibited only small but not systematic variations during the pre-prandial periods. This observation is in agreement with the ischymetric hypothesis which proposes that the decrease of MF inducing the onset of a meal is due not only to the decrease of the glucose utilization but also to the concomitant decrease of the utilization of the three kinds of metabolic substrates.

Animals↗

Iontophoretic investigation of identified SFO angiotensin responsive neurons firing in relation to blood pressure changes.

Activity of 29 histologically identified units in the SFO was recorded in parallel to blood pressure monitoring. The responsiveness of these units to angiotensin II (AII) applied either iontophoretically or via the carotid artery (IC) was investigated together with the capacity of the vasodilator substance NO2- to block the AII response. Fifty-five% of the SFO units responded to iontophoretic application of AII (vs. 27% in the surrounding areas). SFO units were also activated by blood pressure depressions, either as a mirror image (type B) or only restricted to the initial descendent phase of the hypotensive wave (type A). But 8 of the 29 units responded in a mixed A and B fashion, i.e., dramatic firing in the very beginning of the hypotension followed by a sustained moderate response until recovery. Hypertensive spontaneous fluctuations rarely and inconsistently elicited an inhibitory response. An unexpected phenomenon of a hypotensive response following IC injections of low doses of AII was observed and used in this investigation. These observations together with the finding that vasoplegics inhibited unit firing suggest that the SFO is equipped with units able to sense a reduction in local vessels' calibre and fire in relation to it. When activated chemically, electrically or mechanically these units may then trigger hypertensive, antidiuretic and drinking responses.

Angiotensin II↗

Glucagon release after stimulation of the lateral hypothalamic area in rats: predominant beta-adrenergic transmission and involvement of endorphin pathways.

Catheterization of the portal vein and stereotaxic implantation of electrodes in the lateral hypothalamic area (LHA) were performed in normal rats after thiopental anesthesia. Immunoreactive glucagon (IRG) and insulin (IRI), glucose, catecholamines, and beta-endorphin were monitored in portal and peripheral plasma, before and during electrical stimulation of the LHA. The influences on glucose and hormone concentrations of propranolol, phentolamine, atropine, and naloxone infusions were also investigated in similar rats. A basal portoperipheral concentration gradient was found for IRG, IRI, and catecholamines, but not for beta-endorphin. The LHA stimulation induced a significant rise in portal catecholamine, IRG, and glucose concentrations; IRI remained unchanged; the portoperipheral catecholamine gradient was augmented. These alterations were not observed after bilateral splanchnicectomy. Propranolol infusion abolished the LHA-dependent IRG and glucose rises. Naloxone reduced the IRG rise significantly. Phentolamine and atropine did not modify the LHA-induced reactions. These results suggest that the glucagon release which follows LHA electrical stimulation depends mainly on beta-adrenergic transmission by the splanchnic nerves. Opioid peptide receptors may modulate this effect.

Animals↗

LCEC monitoring of 5-hydroxyindolic compounds in the cerebrospinal fluid of the rat related to sleep and feeding.

A new technique which allows for both the chronic withdrawal of CSF and continuous recording of EEG sleep patterns and food intake in the freely moving rat is described. Liquid chromatography with electrochemical detection (LCEC) was used for the direct assay of tryptophan metabolites in the CSF. Both 5-hydroxyindolacetic acid (5-HIAA) and 5-hydroxytryptophan (5-HTP) were easily detectable. However, serotonin (5-HT) levels were relatively low and 5-hydroxytryptophol (5-HTPhol) and N-methylserotonin (N-Me-5HT) were undetectable in several cases. The continuous monitoring of 5-HIAA and 5-HTP indicated stable values throughout the 3-hr experiments during which no food or small meals were consumed. In the rat which consumed a large meal, both 5-HIAA and 5-HTP significantly increased following that meal. This increase in metabolites may be the result of an increased availability of tryptophan to the brain as a result of the meal. Although this study is preliminary, the described technique can provide further information about the possible relationship between behavioral (sleep and/or feeding) changes and the concomitant neurochemical fluctuations.

5-Hydroxytryptophan↗

Hypertension induced by electrical stimulation of the subfornical organ (SFO).

In urethane anaesthetized rats, electrical, low intensity stimulations using bipolar concentric electrodes or monopolar glass pipettes were applied to SFO and to surrounding structure's populations. Blood pressure, recorded from the femoral artery, was systematically and rapidly increased when the electrical, as well as the mechanical (electrode displacements) stimulations were located within the SFO populations. Remote from the SFO, stimulations either were ineffective or produced non reliable responses. SFO cells seen to be involved in the defense against all hydroionic deficiencies, including those of blood pressure.

Animals↗

Lateral hypothalamic control of metabolic factors related to feeding.

States of hunger and satiety are under ischymetric (i.e., rate of cellular energy production) control which depends on both substrate availability and hormonal composition. The latter varies in response to external (olfactory, gustatory and gastrointestinal) stimuli sensed by specific receptors and projected on lateral hypothalamic (LH) units from which departs the descendant control pathway of metabolic glands. This neurohormonal loop is responsible for the anticipatory glycemic and other changes observed during a meal and the preabsorptive "satiation" ending the meal long before the postabsorptive cellular repletion will induce the state of more permanent "satiety". New data on LH "sweet" taste projection and hypothalamo-pancreatic control are shown and strengthen the above view.

Animals↗

Cortical activity and sleep in the rat lateral hypothalamic syndrome.

Continuous EEG recordings were performed in lateral hypothalamic (LH) damaged rats from day 1 post-lesion when totally aphagic and adipsic until complete recovery of their feeding and drinking. During the early post-operative stage (days 1--3 post-lesion), LH rats showed a complete disorganization of their basal EEG which was characterized by two superimposed activities, a constant rapid low voltage activity modulated by high voltage low frequency waves. Except in the case of intense illumination, several arousing stimuli did not affect this activity. By day 4 post-lesion, the two overlapping activities were replaced by less abnormal waves on top of which the first normal sleep spindles appeared. Sleep increased gradually and normal amounts of both slow-wave and paradoxical sleep were observed during 'stage 4' of recovery when rats again ate food and drank water. During this stage, and contrary to normal rats, meal size was correlated only with sleep events occurring within the intermeal interval following the next meal, when most of the ingested nutrients reached the systemic compartment. The effect of sleep of intragastric or intravenous caloric repletion was, at least in part, in agreement with the view of indirect effect of LH lesions on sleep through metabolic impairment. Whatever the mechanism underlying sleep deficits, these are one of the major symptoms of the lateral hypothalamic syndrome.

Animals↗

Circadian sleep and feeding patterns in the rat: possible dependence on lipogenesis and lipolysis.

Sleep and feeding patterns were continuously recorded in rats under intravenous saline (control) and alternating insulin-epinephrine (experimental) infusions. The infusion of insulin (lipogenetic hormone) during the normally light period (0800-1600) replaced by epinephrine (lipolytic hormone) during the normally lipogenetic dark period (1600-0800) resulted in a complete inversion of the normal circadian distribution of sleep and feeding patterns and also of their correlation. Insulin infusion resulted in low blood glucose and glycerol levels whereas epinephrine increased these physiological parameters. Different control conditions showed that the fluctuations of sleep and feeding were dependent on the rate of utilization of the circulating metabolites at the cellular level. These results together with previous data suggest that the relation between sleep and feeding and their concomitant circadian fluctuation are possibly modulated by a common factor, namely the metabolic rate that is influenced by the lipogenesis/lipolysis rate.

Animals↗

Intravenous infusions of nutrients and sleep in the rat: an ischymetric sleep regulation hypothesis.

Unrestrained food-deprived rats received their daily caloric needs through continuous or discontinuous intravenous infusions of specific nutritive substances over a period of 3 consecutive days each, and the effect on sleep monitored by electroencephalogram was examined. Continuous glucose or lipid infusions did not affect the daily sleep quotas. Amino-acid infusion brought about a significant increase in paradoxical sleep (PS), whereas slow-wave sleep (SWS) remained unchanged. Rats that received the highly nutritive composite solution showed significant increase in both SWS and PS. The same increase in SWS and PS was observed when exogenous insulin was coinfused with continuous infusion of glucose or when glucose infusions were discontinuous. These findings suggest that sleep might be related to both the nature and the degree of utilization of the circulating metabolites. A model for the action on sleep of nutrients at the systemic level was proposed; only when substances are metabolized is there a direct effect on sleep mechanisms.

Amino Acids↗