Search PubMed⌕ Search

Biomedical subjects

A Burlet

Publications and source records attributed to A Burlet.

At least 55 records · Page 3Linked to original sources
PubMed1992

Alteration of pituitary-adrenal responses to adrenalectomy by the immunological targeting of CRF neurons.

We previously demonstrated that cellular toxins added to a cytotoxic IgG2a monoclonal antibody to corticotropin releasing factor (CRF-MAb) may specifically penetrate some hypothalamic CRF neurons, after central injection near the paraventricular nuclei. We attempt here to evaluate the consequential effects on the CRF neurons functioning. Such a toxic mix, 4 weeks after its central injection, caused a marked reduction (66%) of the chronic adrenocorticotropic hormone (ACTH) release in response to a bilateral adrenalectomy (7th day). This change was accompanied by a reduction in the CRF concentration (43%) measured in the median eminence. We concluded that specific internalization of toxins, by the way of CRF-MAb, leads to a long-term dysregulation of the CRF synthesis and/or neuronal transport.

Adrenalectomy↗
PubMed1992

Unexpected regulation of hypothalamic neuropeptide Y by food deprivation and refeeding in the Zucker rat.

Neuropeptide Y strongly stimulates food intake when it is injected in the hypothalamic paraventricular (PVN) and ventromedian (VMN) nuclei. In Sprague-Dawley (SD) rats, NPY synthesis in the arcuate nucleus (ARC) is increased by food deprivation and is normalized by refeeding. We have previously shown that the obese hyperphagic Zucker rat is characterized by higher NPY concentrations in this nucleus. NPY might therefore play an important role in the development of hyperphagia. The aim of the present study was to determine if the regulation by the feeding state works in the obese Zucker rat. For this purpose, 10 weeks-old male lean (n = 30) and obese (n = 30) Zucker rats were either fed ad libitum, either food-deprived (FD) for 48 hours or food-deprived for 48 h and refed (RF) for 6 hours. NPY was measured in several microdissected brain areas involved in the regulation of feeding behavior. NPY concentrations in the ARC was about 50% greater in obese rats than in lean rats (p less than 0.02) whatever the feeding state. In the VMN, NPY concentrations were higher in the lean FD rats than in the obese FD rat (p less than 0.001). Food deprivation or refeeding did not modify NPY in the ARC, in the VMN or in the dorsomedian nucleus whatever the genotype considered. On the other hand, food deprivation induced a significant decrease in NPY concentrations in the PVN of lean rats. This decrease was localized in the parvocellular part of this nucleus (43.0 +/- 1.9 (FD) vs 54.2 +/- 2.1 (Ad lib) ng/mg protein; p less than 0.005). Ad lib levels were restored by 6 hours of refeeding. These variations were not observed in the obese rat. The regulation of NPY by the feeding state in the Zucker rat was therefore very different from that described in the SD rats. Strain or age of the animals used might explain these differences. High NPY levels and absence of regulation in obese Zucker rats could contribute to the abnormal feeding behavior of these rats.

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↗
PubMed1992

Specific hypothalamic neuropeptide Y variation with diet parameters in rats with food choice.

Neuropeptide Y (NPY) preferentially stimulates carbohydrate intake rather than fat intake but there is no information on the effects of food choice on the concentration of NPY in the brain. We measured brain NPY concentrations in male adult rats that had to choose between a high fat and a high carbohydrate diet or were fed a control diet for 2 weeks. In rats with food choice, energy intake increased (+17%). NPY levels increased in the parvocellular part (PVNp) of the PVN and decreased in the lateral hypothalamus and were significantly correlated with the carbohydrate-to-fat energy ratio but not with total energy intake. This suggests that hypothalamic NPY might be involved in food choice and that PVNp is important in the regulation of feeding behaviour by NPY.

Animals↗
PubMed1992

Changes in hypothalamic neurotensin concentrations and food intake in rats fed a high fat diet.

Neurotensin (NT), a peptide present both in the brain and in the gastrointestinal tract, has potent anorexigenic effects when centrally injected in rats and is secreted after fat ingestion. High fat diets are often associated with increased energy intake. The aim of this study was therefore to evaluate the role of neurotensin in the feeding behaviour of rats fed on a high fat (HF) diet. Adult Long-Evans rats were fed for two weeks either a control (C) well-balanced diet (n = 10) or a fat-rich diet containing about two-thirds of its energy as fat (margarine and peanut oil; n = 10). Neurotensin was measured by a specific radioimmunoassay in the plasma and in several microdissected brain nuclei involved in the regulation of feeding behaviour. Ingestion of the HF diet induced an increased body weight gain (47.6 +/- 7.7 g (HF) vs. 37.6 +/- 9.3 g (C); P less than 0.05) and an increased energy intake (+ 7.2%; P less than 0.05). Plasma fasting NT concentrations were not affected by the HF diet. In the hypothalamus, significant decreases in NT concentrations were measured in the HF rats in two nuclei important in the regulation of food intake, i.e. the paraventricular nucleus (1.72 +/- 0.16 (HF) vs. 2.27 +/- 0.15 (C) ng/mg protein; P less than 0.05) and the lateral hypothalamus (1.87 +/- 0.16 (HF) vs. 2.37 +/- 0.19 (C) ng/mg protein; P less than 0.05). On the other hand, no variations were measured in the ventral tegmental area, an important site for the metabolism and regulatory action of neurotensin and in other hypothalamic nuclei.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Rapid and localized alterations of neuropeptide Y in discrete hypothalamic nuclei with feeding status.

Neuropeptide Y (NPY) is believed to regulate the normal eating behavior and body weight in rats via central mechanisms. We have investigated whether NPY, which stimulates food intake, may in turn be modified by the nutritional state of the animals. Thus the impact of food deprivation (FD) (48 h) and subsequent refeeding on the levels of NPY in discrete hypothalamic areas was examined in this study. The results showed site specific change in only 3 of 7 hypothalamic sites. A 5-fold increment in NPY was reported in the paraventricular nucleus (PVN) and a 10-fold increase was observed in the arcuate nucleus-median eminence (ARC-ME). While subsequent refeeding for 6 h reversed the effect of FD in the ARC-ME, the levels of NPY in the PVN remained high in the refed rats. The perifornical lateral hypothalamus displayed a different pattern, namely, a significant increase in NPY content in refed as compared to satiated and deprived rats. The NPY levels in 4 other hypothalamic sites, namely, the dorsomedian, ventromedian, supraoptic and suprachiasmatic nuclei, and two extrahypothalamic sites, namely caudate nucleus and nucleus accumbens, showed total resistance to any change following deprivation and refeeding. These data emphasize the important and specific role of the paraventricular and arcuate nuclei in NPY's regulation of food intake and provide support for the idea that the variations of hypothalamic NPY after food deprivation reflect a specific physiological response of feeding regulatory system to alterations in the animal nutritional state and body weight.

Animals↗
PubMed1990

Hypothalamic neuropeptide Y (NPY) in obese Zucker rats: implications in feeding and sexual behaviors.

Neuropeptide Y (NPY), a peptide of the pancreatic polypeptide family, is actually considered to be the most potent stimulator of food intake in rats when centrally injected. It has also suppressive effects on several components of sexual behavior. It was measured in discrete microdissected brain nuclei in obese hyperphagic Zucker fa/fa rats also characterized by a deficient reproductive function, as well as in their lean homozygous (Fa/Fa) and heterozygous (Fa/fa) counterparts. When compared with the lean (Fa/Fa) rats, NPY concentrations were significantly increased in the obese rats in the arcuate nucleus-median eminence (ARCME, +300%), in the paraventricular (PVN, +60%), suprachiasmatic (SCH, +90%), accumbens (+100%) and supraoptic (+40%) nuclei, as well as in the median preoptic area (MPOA, +70%). As PVN is one of the most important nuclei involved in the control of food intake and one site of NPY action, the high levels found in this nucleus might be a major component at the origin of hyperphagia in the obese animals. Food intake might be overstimulated by a sustained production of NPY as shown by the high concentrations found in the ARCME. NPY might also intervene in the pattern of food intake, for NPY contents were also largely modified in the SCH, the nucleus regulating feeding periodicity and in the MPOA, which is possibly involved in the regulation of energy balance. Finally, as the MPOA is the only site of action of NPY on sexual behavior, the higher levels measured in this area might contribute to the defective reproductive function of the obese Zucker fa/fa rat.

Animals↗
PubMed1990

Ingestive behaviors of the rat deficient in vasopressin synthesis (Brattleboro strain). Effect of chronic treatment by dDAVP.

Spontaneous manipulator and locomotor activities, food and fluid intake have been recorded from rats suffering from a genetic lack of central vasopressin (VP) synthesis (Brattleboro strain, DI), their heterozygous litter mates (HZ) or Long Evans (LE) rats. The daily patterns of activities did not differ, except for their drinking behavior. This was mainly associated with food intake during the dark period with LE rats but was distributed equally during light and dark periods with DI rats. HZ rats showed a behavioral heterogeneity, some of them following the daily pattern of LE rats, and others, that of DI rats. The daily feeding pattern was identical in the three genotypes but the selection between two isocaloric contrasted diets was different. When they were fed ad lib, HZ and DI rats consumed less carbohydrate than LE rats, the protein intake being unchanged. On the contrary, when the DI rats were only fed during the dark period, they ate more carbohydrate than LE rats. The peripheral infusion of a V2 AVP agonist (dDAVP) restored a normal hydric balance in DI rats but failed to modify the diet selection. These data show that in the rats, the lack of central VP synthesis disturbs both the selection of diets and the efficiency of the satiety signals. These disturbances were unchanged by the peripheral VP treatment which suggested the direct involvement of the central release of the neuropeptide.

Animals↗
PubMed1990

Influence of diet composition on food intake and hypothalamic neuropeptide Y (NPY) in the rat.

Ingestion of a high carbohydrate (HC) or high fat (HF) diet induces obesity in association or not with modifications of the feeding behaviour. Effects of diet composition on NPY, a powerful stimulant of weight gain and food intake (particularly carbohydrates), are not known. That is why we measured NPY in 10 microdissected brain nuclei of rats fed either a HC diet (69% of energy from carbohydrates), a HF diet (68% of energy from fat) or a control well-balanced diet (54% of energy from carbohydrates; 30% of energy from fat) during a 14-day period. Total caloric intake was significantly greater (+12%) in rats fed on the HF diet than in the control and HC rats. HF rats also gained more weight than the two other groups (47.5 +/- 2.4 g vs 37.6 +/- 2.6 g (control) and 29.1 +/- 1.4 g (HC); p less than 0.001). NPY variations were restricted to two hypothalamic areas. In the parvocellular part of the paraventricular nucleus, NPY was smaller with the HC diet than with the HF diet (42.1 +/- 2.3 vs 49.5 +/- 2.7 ng/mg protein; p less than 0.05). A decrease was observed in the lateral hypothalamus with the HF diet when compared with the control diet (11.3 +/- 0.7 vs 14.6 +/- 1.1 ng/mg protein; p less than 0.05). No variations were observed either in other hypothalamic nuclei such as arcuate, dorsomedian, ventromedian or suprachiasmatic nuclei or in extra-hypothalamic areas such as the ventral tegmental area or submamillary bodies.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Hyperphagia in obesity is associated with a central peptidergic dysregulation in rats.

Hyperphagia and obesity are often associated, and the origins of the biochemical modifications leading to these syndromes might be in the hypothalamus. Indeed, food intake is regulated by numerous neuropeptides in various hypothalamic nuclei, including the paraventricular (PVN), arcuate (ARC), ventromedian (VMN) and suprachiasmatic (SCH) nuclei. Among these peptides, neuropeptide Y (NPY) is the most potent inducer of food intake whereas neurotensin (NT) decreases food intake. We measured these two peptides in microdissected hypothalamic nuclei in obese Zucker rats that ate 30% more food than their lean counterparts. Neuropeptide Y and neurotensin levels varied in opposite directions: In the hyperphagic obese Zucker rats, the NPY concentrations were significantly greater than those in the lean normophagic rats in the ARC (+30%), PVN (+60%) and SCH (+94%) nuclei, whereas the NT levels were significantly lower in the ARC (-40%), PVN (-31%) VMN (-66%) and SCH (-47%) nuclei. Both these variations tend to increase food intake. Feeding periodicity might also be modified because large variations of the two peptides have been measured in the supra-chiasmatic nucleus, which is considered the most important regulator of feeding rhythm. The results reinforce the hypothesis that hyperphagia in obesity is associated with a biochemical modification in the central nervous system because the peripheral status of NT and NPY was not modified in the obese rats. Because levels of other hypothalamic peptides, such as opioid peptides and somatostatin, are also slightly modified, it can be concluded that hyperphagia in obesity is associated with a central peptidergic dysregulation. Research on drugs reacting specifically with the receptor of these peptides might have interesting implications for the treatment of hyperphagia and, therefore, of obesity.

Animals↗
PubMed1989

Neurotensin in microdissected brain nuclei and in the pituitary of the lean and obese Zucker rats.

Neurotensin (NT) is a tridecapeptide common to the gastrointestinal tract and central nervous system which suppresses food intake when centrally injected in various regions of the hypothalamus. We measured neurotensin levels in several microdissected brain nuclei as well as in the pituitary in 10 obese hyperphagic Zucker (fa/fa) rats, 9 heterozygous Fa/fa and 5 Fa/Fa lean rats. The greatest NT concentration and content were observed in the anterior lobe of the pituitary in the median eminence and in the lateral preoptic area (500 to 1000 pg/area, 3 to 5 ng/mg protein). NT was also detected in the median preoptic area, paraventricular (PVN), supraoptic, ventromedian nuclei (VMN) (about 250 pg/nucleus, 1.5 to 2 ng/mg protein). The smallest amounts were found in the suprachiasmatic (SCH) and accumbens nucleus (about 100 pg/nucleus, 1 ng/mg protein) and the peptide was absent in the cortex. NT content in the obese rat was significantly lower in all brain nuclei examined except the accumbens nucleus. This was most evident in the three nuclei involved in the regulation of feeding behaviour: PVN (276 +/- 38 (Fa/Fa) vs 188 +/- 15 (fa/fa) pg/nucleus, P less than 0.05), VMN (226, +/- 21 (Fa/Fa) vs 75 +/- 22 (fa/fa) pg/nucleus, P less than 0.001), and SCH (98 +/- 14 (Fa/Fa) vs 52 +/- 11 (fa/fa) pg/nucleus, P less than 0.05). There was no difference in the pituitary lobes between lean and obese rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Vasopressin neuron is the target of monoclonal antibodies raised against vasopressin-neurophysin injected in vivo.

Monoclonal antibodies (MAbs) raised against the neurophysin (NP) specifically synthesized with vasopressin (VP, VP-NP) were injected into the paraventricular nucleus (PVN) of the rat hypothalamus. Their fate was studied by immunocytochemistry from 1 min to 3 h after the end of injection. It could be demonstrated that the VP-NP MAbs penetrated in vivo into some magnocellular neurons of the injected PVN and were transported ipsi- and contralaterally in individual neurons and in accessory magnocellular groups. When the time after injection was longer than 15 min, the VP-NP MAbs were also carried in the fibers of the median eminence. The prior treatment of rats with colchicine did not prevent the uptake of VP-NP MAb in the neurons but inhibited the transport towards the eminential fibers, the individual neurons and accessory groups. The detection of the PVN endogenous peptides (VP and oxytocin) on the same brain sections indicates that the neuronal uptake was specific. It only occurred in the neurons which synthesized VP and never appeared in the brain of rats suffering from a genetic defect of the central VP synthesis (Brattleboro rat). These data support the hypothesis of the location on the cell surface of the VP-NP precursor in magnocellular neurons which synthesize VP. This membrane signal identifies the neuron and allows the immunological recognition of the neurosecretory neurons in vivo.

Animals↗
PubMed1985

Immunohistochemical localization and radioimmunoassay of corticotropin-releasing factor in the forebrain and hypophysis of the frog Rana ridibunda.

The distribution of immunoreactive corticotropin-releasing hormone (CRF) in the forebrain and pituitary of the frog Rana ridibunda was studied by means of specific radioimmunoassay and immunohistochemistry using the indirect immunofluorescence and the peroxidase-antiperoxidase techniques. Relatively high concentrations of CRF-like material were found in both chiasmatic and infundibular regions of the hypothalamus (352 +/- 11 and 422 +/- 36 pg, respectively). Large amounts of CRF were also found in neurointermediate lobe extracts. Standard curves of synthetic CRF and the dilution curves for hypothalamic or neurointermediate lobe extracts were parallel. After Sephadex G-75 gel filtration, CRF-like immunoreactivity eluted in a single peak, in the same position as synthetic ovine CRF. Reversed-phase high-performance liquid chromatography of the material purified on Sephadex G-75 revealed 5 components with CRF-like immunoreactivity. The major peak had a retention time of 22 min as compared to 25.4 min for ovine CRF and 36 min for rat CRF. The detection of CRF-like immunoreactivity in neurons was facilitated by colchicine pretreatment of the frogs. The great majority of the CRF-positive perikarya were seen in the ventral region of the preoptic nucleus. A few scattered perikarya were also observed in the dorsal preoptic nucleus and in the retrochiasmatic region. Immunoreactive fibers were found in the infundibular nucleus and in various extrahypothalamic zones. CRF-containing neurons were apparently distinct from mesotocinergic and vasotocinergic neurons. A large number of immunoreactive nerve fibers were observed in the median eminence in close contact with the capillaries of the pituitary portal plexus and in the neural lobe. A few CRF-positive fibers were detected in the intermediate lobe, whereas the distal lobe was totally negative. These results show that the diencephalon and pars intermedia-nervosa of the frog contain a peptide immunologically related to mammalian CRF.

Animals↗
PubMed1984

Comparative immunoelectron microscopic localization of corticotropin-releasing factor (CRF-41) and oxytocin in the rat median eminence.

Comparative ultrastructural localization of corticotropin-releasing factor (CRF) and oxytocin was performed in the rat median eminence of Long Evans and Brattleboro rats. The peroxidase-antiperoxidase technique used on serial ultrathin sections revealed CRF and oxytocin neurosecretory granule colocalization in the same fibers of the internal layer running towards the posterior pituitary. It is probable that both these peptides coexist in the same granules. In the Brattleboro rats, while genetically lacking vasopressin, CRF was nevertheless shown to be present. In these rats, as was demonstrated in the Long Evans rats, CRF distribution paralleled that of oxytocin only in the internal zone of the median eminence.

Animals↗
PubMed1984

[The co-localization of neurohypophysis peptides and the corticotropin-releasing factor in the rat brain. Contribution of morphometric analyses].

Using adjacent serial brain sections, a morphometric method has been developed for analysing the coexistence of the neurophysial hormones, vasopressin (VP) and oxytocin (OT), with their specific neurophysins (N). A significative correlation was found between the immunoreactive areas stained with (1) anti-VP and anti-N-VP sera, and between the immunoreactive areas detected with anti-OT and anti-N-OT antibodies. Besides, the immunoreactive areas stained with (1) anti-VP and anti-OT antibodies, (2) anti-N-OT and anti-VP antibodies, (3) anti-N-OT and anti-N-VP antibodies or (4) anti-OT and anti-N-VP antibodies were totally independent. A different method projecting the microscope images on a reference grid with a camera lucida permitted to quantify the coexistence of an ovine corticotropin-releasing factor-related-peptide (41-CRF) with OT in the paraventricular neurons of the Brattloro rat brain. In these animals, the same method applied after total hypophysectomy demonstrated that the neurons synthezising simultaneously 41-CRF and OT projected their axons to the neurohypophysis; the same operation increased the relative number of neurons containing 41-CRF only; it can be supposed that they originated the infundibular terminals.

Animals↗
PubMed1983

Comparative immunocytochemical localization of corticotropin releasing factor (CRF-41) and neurohypophysial peptides in the brain of Brattleboro and Long-Evans rats.

The localization of CRF-41 related peptide was studied in the brain and posterior pituitary of the homozygous rats for the inherited diabetes insipidus (Brattleboro strain, DI) and of the Long-Evans rats (LE) as control. It was compared to the distribution of vasopressin (AVP), oxytocin (OXY) and OXY-neurophysin (N I). In both strains, CRF-41 was identified in two morphologically distinct systems: one was a hypothalamoneurohypophysial system simultaneously containing CRF-41, OXY and N I; the other was a hypothalamoinfundibular system carrying CRF-41 only. CRF containing neurons were located in the periventricular area of the anterior hypothalamus, in the retrochiasmatic part of the supraoptic nuclei (SON) and, for some of them, in the antechiasmatic part of SON. CRF immunostainings were enhanced by colchicine treatment in LE rats and by DDAVP therapy in DI rats.

Animals↗