Biomedical subjects

B Fernette

Publications and source records attributed to B Fernette.

9 recordsLinked to original sources

PubMed2007

Mineralocorticoid pretreatment enhances angiotensin II-induced neuronal excitation but not salt drinking in male Fischer rats.

Central administration of angiotensin (Ang) II stimulates thirst and sodium intake via the AT-1 receptor. Mineralocorticoid pretreatment enhances Ang II-induced drinking of hypertonic salt solutions (i.e. the synergy theory) in Wistar and Sprague-Dawley rats. Electrophysiological experiments using iontophoretic application of Ang II, and the AT-1 receptor specific nonpeptide antagonist losartan, have shown excitation of neurones in the preoptic/medial septum region of urethane anaesthetised male Wistar rats. Deoxycorticosterone acetate (DOCA) pretreatment further enhanced this neuronal excitation to Ang II and reduced the responses to losartan. This generated the hypothesis that DOCA-enhanced Ang II-induced neuronal excitation was necessary for the enhanced salt intake of synergy theory. We tested this hypothesis in Fischer 344 rats that are known to have a low basal salt appetite and reduced sensitivity for i.c.v. Ang II. We compared the effect of DOCA pretreatment on i.c.v. Ang II-induced water and 2% NaCl intake in behaving adult male, Fischer rats, as well as preoptic/medial septum region neuronal responses to Ang II and losartan, using a seven-barrelled micro-iontophoretic electrode sealed to a recording electrode in urethane anaesthetised, male Fischer rats. Two groups were used: one pretreated with DOCA (0.5 mg/day for 3 days) and the other comprising controls, treated with isotonic saline. Ang II applied iontophoretically increased activity in 31% of the spontaneously active neurones. Following DOCA pretreatment, the responsiveness to Ang II (when applied after aldosterone) was increased. By contrast, in the behaving animals, water and 2% NaCl intake in response to i.c.v. Ang II were not enhanced by DOCA pretreatment. These results do not support the working hypothesis but could be interpreted as evidence for the existence of two separately modulated central Ang II systems: one responding to mineralocorticoids with increased neuronal activity and the other responsible for the Ang II-induced sodium appetite in conscious rats.

Action Potentials↗

PubMed2005

Antenatal glucocorticoids blunt the functioning of the hypothalamic-pituitary-adrenal axis of neonates and disturb some behaviors in juveniles.

Antenatal glucocorticoids are highly effective in preventing respiratory distress of premature babies but can induce physiological and behavioral disturbances in young infants as well as in animals. Therefore, the hypothalamic-pituitary-adrenal (HPA) axis of rat neonates, and the consequences on behavioral development of offspring have been studied after five antenatal injections of dexamethasone (DEX) or vehicle. DEX decreased offspring body weight at birth, and significantly delayed the normal growth for the first 3 weeks of life. This paralleled diminished behavioral performances measured on postnatal day 3 (righting reflex) and postnatal day 10 (grasping test). Circulating levels of adrenocorticotrophin (ACTH) and corticosterone were significantly decreased on postnatal day 1 and this was related to a diminution of HPA axis activity shown by the decrease of central expression of corticotropin releasing hormone (CRH) mRNA, immunoreactive content in paraventricular neurons (PVN) and in the median eminence endings were significantly decreased. On the other hand, expression of another secretagogue of ACTH, arginine vasopressin (AVP), was differently affected in the PVN parvocellular neurons of offspring of the DEX group since AVP mRNA increased whereas immunoreactive content of the PVN parvocellular neurons was lowered. Simultaneously, the co-production of AVP and CRH in PVN neurons was stimulated. This can support the view that antenatal DEX reached the fetus and produced some damage which did not parallel that induced by prenatal stress of the pregnant females, especially the low body weight of offspring. The harmful consequence of antenatal DEX treatment was not restrictively due to the blunting of the HPA axis but also to the low body weight, which disturbed behavioral performances for the first weeks of life and could participate in other disorders in adult life.

Adrenocorticotropic Hormone↗

PubMed2002

Galanin receptor antagonists decrease fat preference in Brattleboro rat.

The Brattleboro rat eats spontaneously 46% of its diet per day in fat when given a choice of carbohydrate, protein and fat. An overexpression of galanin (GAL) has been also observed in the hypothalamic paraventricular nuclei (PVN). This associative correlation has led to a hypothesis of a functional relation between central galanin expression and the preference for a lipid diet. In the present experiments, the effects of two GAL receptor antagonists, C7 and galantide, on fat consumption and central overexpression of GAL were investigated. Both antagonists were injected into either the cerebral ventricles or directly above the PVN, and the diet consumption followed for the subsequent 24h. C7 decreased significantly fat consumption when injected into the ventricles or directly above the PVN. In contrast, galantide must be injected above the PVN to show the same effect. However, the two antagonists did not modify GAL mRNA expression in the PVN when they were injected 2h before sacrifice. These experiments confirm a functional link between the preferential consumption of fat and hypothalamic Galanin; different subtypes of the GAL receptor are probably involved, since both Galanin antagonists were differently efficient in decreasing spontaneous fat selection of the Brattleboro rat.

Animals↗

PubMed2002

Neonatal maternal deprivation modifies feeding in response to pharmacological and behavioural factors in adult rats.

Neonatal maternal deprivation permanently modifies the hypothalamo-pituitary-adrenal (HPA) axis and other neurobiological and behavioural parameters in rats. The HPA axis plays a central role in the control of feeding, and participates in the anorexigenic action of dexfenfluramine and restraint stress, and in the orexigenic action of a cafeteria diet. Therefore, we investigated whether maternal deprivation modifies feeding responses to these factors. Experimental pups were separated for 24h from the mother 5 or 14 days after birth. The anorexigenic response to both dexfenfluramine and restraint stress was increased, and body weight as well as subcutaneous adipose tissue gain induced by cafeteria diet was higher in early deprived adult rats. However, these effects were dependent on the time of maternal deprivation. According to our predictions, the feeding response of maternally deprived rats to anorexigenic and orexigenic agents was altered, which is probably partly due to an altered HPA function, but the participation of the serotonergic, the opioid and/or the dopaminergic system cannot be ruled out. Additional studies are needed to detail precisely the neurobiological substrates of modified feeding behaviour of maternally deprived animals. This early stress paradigm altering feeding behaviour could become an interesting model for research into human eating disorders.

Age Factors↗

PubMed2001

Postnatal maternal deprivation produces long-lasting modifications of the stress response, feeding and stress-related behaviour in the rat.

The hypothalamo-pituitary-adrenal (HPA) axis plays a central role both in the regulation of the stress response, and in the control of feeding behaviour. Sensitivity of the HPA axis to respond to stress varies both during ontogeny and between individuals, and can be altered by neonatal events. The aim of our experiments was to determine whether early events that affect the HPA axis could also induce persistent modifications in food intake (quantitatively and qualitatively), as well as alterations of anxiety-related behaviour. Twenty-four-hour maternal deprivation was introduced at two different periods of HPA maturation, on day 5 (DEP5) or day 14 (DEP14) after birth. Sequential measurements of plasma levels of adrenocorticotropin hormone (ACTH) and corticosterone showed that this deprivation altered the HPA axis of adults; the response to restraint stress was prolonged in DEP5 and a higher ACTH peak appeared in DEP14. The neonatal stress also produced long-lasting modifications of rat behaviour, as DEP14 adults became more anxious. Standard food intake decreased in both groups of deprived rats. Diet preferences also changed, as carbohydrate intake decreased in DEP5 rats. Corticosteroid receptor binding did not vary in the hippocampus of the deprived rats. The modifications of the stress response and the behaviour parameters could be due to the alteration of corticosteroid receptors in the hypothalamic paraventricular nucleus and/or corticotropin-releasing hormone or vasopressin function, but these parameters have yet to be determined. This early stress paradigm altering feeding behaviour could become an interesting model for research into human eating disorders.

Adrenocorticotropic Hormone↗

PubMed1997

Arginine vasopressin (AVP) depletion in neurons of the suprachiasmatic nuclei affects the AVP content of the paraventricular neurons and stimulates adrenocorticotrophic hormone release.

Arginine vasopressin (AVP) produced in the hypothalamic suprachiasmatic nuclei (SCN) plays a role in establishing neuroendocrine rhythms and, in particular, in regulating the corticotrope axis rhythm. It has recently been shown that AVP from SCN inhibits corticosteroid release. In order to investigate the influence of suprachiasmatic AVP on the different peptidergic systems through the hypothalamus, SCN neurons containing AVP were functionally lesioned by using toxins associated with a cytotoxic monoclonal antibody (MAb) raised against AVP. Six days later, the AVP contents and AVP mRNA were measured in different hypothalamic and extrahypothalamic sites. Adrenocorticotrophic hormone (ACTH) concentration was also measured in plasma. Microinjection of the AVP-MAb/toxin mixture into SCN brought about a significant decrease in the AVP expression in SCN. This is demonstrated by the decrease in the AVP immunoreactive content (24%, P < 0.01) and the decrease of AVP hybridized mRNA (33%, P < 0.01). This points to the efficiency of the microinjection in decreasing the production of AVP in the injection area. Modifications of the AVP contents in the two subdivisions of the hypothalamic paraventricular nucleus (PVN) were also observed. AVP contents decreased in the parvocellular subdivision (pPVN); this is coherent with the AVP depletion in SCN since pPVN is the major site of the SCN hypothalamic efferences. AVP content and AVP mRNA increased in the magnocellular subdivision (mPVN); this also confirms the difference in AVP synthesis regulation according to the PVN subdivisions. The microinjection did not modify AVP expression in supraoptic nuclei or oxytocin (OT) immunoreactive content in the main hypothalamic OT containing sites. Plasma ACTH values were double (P < 0.02) the values measured under non-specific IgG treatment 10 hr after lights on. This probably resulted from the stimulation of the hypothalamo-pituitary-adrenal system since corticotrophin-releasing hormone (CRH) mRNA increased simultaneously by 24% (P < 0.05) in the PVN and the immunoreactive CRH content of the median eminence significantly decreased (26%, P < 0.05). Overall, our data confirm that AVP produced in the SCN inhibits the CRH-adrenocorticotrope axis in normal conditions, probably because of SCN projections of AVP neurons on the PVN.

Adrenocorticotropic Hormone↗

PubMed1995

The immunological impairment of vasopressin (AVP) neurons into paraventricular nuclei modifies AVP expression in suprachiasmatic nuclei.

A monoclonal antibody (MAb) to vasopressin (AVP) inhibits the synthesis and the release of AVP when injected near the AVP-producing neurons. In the present experiments, the AVP-MAb was microinjected near the paraventricular (PVN) or the supraoptic (SON) neurons of the rat hypothalamus and the AVP expression was measured in the suprachiasmatic nuclei (SCN). When microinjected near PVN, the AVP-MAb modified the AVP mRNA studied by in situ hybridization, and the AVP immunoreactive content of SCN, whereas it failed to show some effect when injected near SON. This confirms the privileged relationships between AVP-producing neurons in SCN and PVN.

Animals↗

PubMed1995

The immunological impairment of arcuate neuropeptide Y neurons by ricin A chain produces persistent decrease of food intake and body weight.

Neuropeptide Y is demonstrated as a potent orexigenic peptide when injected into the rat hypothalamic paraventricular nuclei. The neuropeptide Y innervation of paraventricular nuclei originates from both hypothalamic arcuate nuclei and brainstem neurons, whose specific role in the control of food intake is still under discussion. To assess the role of the arcuate neuropeptide Y in the regulation of food intake, we propose a new method for immunologically impairing the neuronal secretion of neuropeptide Y from a unique brain site. The monoclonal antibody to the neuropeptide Y precursor epitope, the C-flanking peptide, was microinjected with two cellular toxins (the ricin A chain and the monensin) into the hypothalamic arcuate nuclei or paraventricular nuclei. One microinjection into the arcuate nuclei reduced the food intake and body weight gain for 10 days. It prevented the food intake stimulation usually induced by a 12 h food deprivation. This decrease of food intake was not due to the aversive properties of monoclonal antibody or cellular toxins, or the immunoneutralization of the biologically active neuropeptide Y, because (i) the acute effect of the microinjection into the arcuate nuclei promoted a transient increase of the food intake likely induced by a strong release of neuropeptide Y from the arcuate neurons which were immunologically damaged, and (ii) the C-flanking peptide monoclonal antibody binds neither neuropeptide Y nor its receptors. The microinjection was inefficient when C-flanking peptide monoclonal antibody was replaced by non-specific rat immunoglobulins or when the C-flanking peptide monoclonal antibody/toxins mixture was injected into the paraventricular nuclei. The data bring further arguments in two domains.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Long-term reduction of vasopressin excretion induced by the central injection of an immunoconjugate (antibody to vasopressin linked to ricin A chain).

We have previously demonstrated that vasopressin-producing neurons are the target of monoclonal antibodies to vasopressin microinjected into the brain tissue. At the same time, this central microinjection of vasopressin-monoclonal antibody into the supraoptic nuclei produced hydro-osmotic disorders mimicking the effects of a central diabetes insipidus. In order to investigate the increase in both duration and amplitude of the biological effects seen after the injection of vasopressin-monoclonal antibody, an immunoconjugate was constructed with the vasopressin-monoclonal antibody IgG1k isotype and the cytotoxic part of the ricin molecule, the ricin A chain. The biological parameters, such as diuresis and urine osmolality which are directly regulated by vasopressin, and vasopressin excretion, were measured after the central injection of this immunotoxin/immunoconjugate. The consequences of immunotoxin injection were also studied when immunotoxin was co-injected with monensin (50 nM) which has been shown to decrease the intracellular degradation of immunotoxin, and plasma complement, which has been shown to increase the neuronal uptake of immunotoxin. Single injection of immunotoxin near the hypothalamic supraoptic nuclei significantly increased diuresis and decreased vasopressin excretion. However, these effects were only transient and disappeared 24 h later. Four successive injections of immunotoxin (one per day) with monensin induced a decrease of vasopressin excretion which was still observed after a resting period of four days after the fourth injection. The long-term reduction of vasopressin excretion was induced in rats receiving four successive injections of a mixture consisting of immunotoxin with monensin and plasma complement. In such experiments, the vasopressin content of urine remained low (55% under the baseline value), two weeks after the fourth injection of immunotoxin. At the same time, the diuresis was increased (80% above the baseline value) and urine osmolality lowered (45% under the baseline value). When non-specific IgG replaced specific antibody, vasopressin excretion, diuresis as well as urine osmolality were unchanged. The results of this study demonstrated that the use of a specific immunotoxin results in a local interference with the vasopressinergic neurons and induces a long-term reduction of vasopressin secretion.

Animals↗