Search Results - (Author, Cooperation:M. J. Mercier)

2015-11-19

Nature Publishing Group (NPG)

0028-0836

1476-4687

Biology

Chemistry and Pharmacology

Medicine

Natural Sciences in General

Physics

2015-05-08

Nature Publishing Group (NPG)

0028-0836

1476-4687

Biology

Chemistry and Pharmacology

Medicine

Natural Sciences in General

Physics

1365-2826

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Oxytocin- and vasopressin-binding sites were detected by autoradiography on films and on emulsion-coated sections of rat brains using highly selective [125|]-labelled oxytocin and vasopressin antagonists. Two distinct areas with high concentrations of oxytocin-binding sites were detected in the bed nucleus of the stria terminalis: 1) the principal encapsulated nucleus and the associated cell-sparse zone in the posterior medial part, and 2) the oval nucleus in the anterior lateral part. A weak diffuse labelling was, in addition, detected around the oval nucleus in the anterior lateral and anterior dorsal areas. The vasopressin-binding sites were restricted to the anterior lateral part of the bed nucleus of the stria terminalis where they were highly concentrated in the juxtacapsular nucleus and present with lower density in a discrete cell group dorsal to the oval nucleus.Autoradiographic analyses of the bed nucleus of the stria terminalis from pregnant, lactating and ovariectomized rats (oestradiol treated or not) indicated that only the oxytocin-binding sites in the principal encapsulated nucleus and the associated cell-sparse zone were oestrogen-dependent. These observations are in agreement with earlier data suggesting that the two major divisions of the bed nucleus of the stria terminalis are involved in distinct regulations. The anterior lateral part, including the oval nucleus in which oxytocin receptors are not oestrogen-dependent, is, rather, involved in central autonomie regulations. The posterior medial part, where oestrogen-dependent oxytocin receptors are concentrated in the principal encapsulated nucleus and the associated cell-sparse zone, is implicated in neuroendocrine regulations and in reproductive behaviour.

Electronic Resource

1365-2826

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Several regions of the forebrain possess high densities of oxytocin (OT)-binding sites including the bed nucleus of the stria terminalis (BST) and lateral septum (LS). In order to examine whether these regions participate in the central facilitation of the milk ejection reflex by OT, microinjections of OT (1 ng in 100 nl containing Janus Green dye) were made into the BST (13 tests) or LS (9 tests) of anaesthetized, suckled rats, while recording the electrical activity of OT neurons in the contralateral supraoptic nucleus. Histological localization of injection sites using Janus Green demonstrated that all BST injections were close to the anterior commissure, and LS injections were all located in the ventral division of the LS. Film autoradiographic visualization of OT-binding sites (in 7 tests using [125I]OT antagonist) confirmed that the BST and LS injections were located within regions of high OT binding. Injections into both regions facilitated the milk ejection reflex by increasing either the frequency and/or amplitude of OT neuron bursts, or by triggering bursts in animals that previously had shown no milk ejection responses; the mean number of milk ejections in the 30 min before and after injection increasing from 1.6·0.5 to 3.6·0.5 for BST and from 1.5·0.6 to 3.9·0.4 for LS. The OT microinjections had a more variable effect on background activity of OT neurons, increasing firing in some cases and not in others. This facilitatory effect was similar to that induced by microinjections into the lateral ventricle, but was smaller and delayed compared to that induced by injection into the third ventricle (9 tests), possibly due to unilateral activation of target sites. The facilitatory effect was unlikely to have been due to diffusion of OT into the ventricle, since injections into control sites (striatum and thalamus) at similar distances from the ventricle (9 tests) had no facilitatory effect (number of bursts during 30 min before and after injection; 2.2·0.5 and 1.8·0.5, respectively). These data suggest that limbic structures (BST and LS) participate in the action of central OT on the pattern of milk ejections in the suckled rat.

Electronic Resource

1365-2826

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

The goal of the present experiments was to analyse the binding of oxytocin (OT) and vasopressin (VP) in the hypothalamo-neurohypophyseal system to determine whether [3H]OT and [3H]VP binding in this system involved interaction with receptor sites or with neurophysins. Using quantitative autoradiography, several experiments were performed to compare [3H]OT- and [3H]VP-binding characteristics in this system and in brain areas containing identified receptor sites. Saturation experiments indicated much lower affinity of [3H]OT and [3H]VP binding in the magnocellular nuclei and neural lobe than on brain receptors. Competition experiments using selective ligands indicated interaction with neurophysins rather than with receptors in the hypothalamo-neurohypophyseal system. This system was never labelled in the presence of a [125I]OT antagonist, a selective OT receptor ligand. In contrast with receptors elsewhere in the brain, the magnocellular nuclei were labelled by [3H]OT and [3H]VP in the absence of MgCI2. In the pituitary neural lobe, density of binding sites was moreover obviously related to the amount of neurosecretory granules, as seen in acutely dehydrated rats. Taken together, these data strongly suggest that in the hypothalamo-neurohypophyseal system [3H]OT and [3H]VP bind to neurophysins rather than to specific receptors.

Electronic Resource

1365-2826

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

The localization at the cellular level and the regulation by progesterone of the estrogen-sensitive oxytocin binding sites was studied in the rat telencephalon and the hypothalamus by using quantitative film-autoradiography and histoautoradiography. Male rats (castrated or not) and ovariectomized females (estradiol supplemented or not) were used to characterize these sites and to precise their localization. They were detected in the striatal cell bridges, the olfactory tubercle, the principal nucleus of the bed nucleus of the stria terminalis and the medial nucleus of the amygdala of the telencephalon and in the medial preoptic, the ventromedial and the ventral premammillary nuclei of the hypothalamus. Estrogen administration in addition induced expression of oxytocin binding sites in the major island of Calleja, the anterior hypothalamic area and the terete nucleus. The density of the estrogen-sensitive oxytocin binding sites varied during the estrous cycle, but differently in the telencephalon and the hypothalamus. in the telencephalon it peaked at proestrus 9 h and was already decreased at proestrus 21 h, whereas in the hypothalamus it was similarly high at proestrus 9h and proestrus 21 h, suggesting the intervention of progesterone in the regulation of the hypothalamic estrogen-sensitive oxytocin binding sites.

Electronic Resource

1365-2826

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

In the magnocellular nuclei of the hypothalamus, there is a rich vascular network for which the function remains to be established. In the supraoptic nucleus, the high vascular density may be one element, which together with the water channel aquaporin-4 expressed in the astrocytes, is related to a role in osmoreception. We tested the osmoreception hypothesis by studying the correlation between vascular and cellular densities in the paraventricular nucleus and the supraoptic nucleus. Whether aquaporin-4 is likely to contribute to osmoreception was tested by studying the distribution in the magnocellular nuclei of the hypothalamus. The high vascular density may also reflect a high metabolic activity due to the synthesis of vasopressin and oxytocin. This metabolic hypothesis was tested by studying the regional cytochrome oxidase histochemistry, the local cerebral blood flow, and the density of glucose transporter type-1 in the supraoptic and paraventricular nuclei. All the magnocellular nuclei were characterized by an extended and intense aquaporin-4 labelling and a weak cytochrome oxidase histochemistry. The highest vascular density was found in the supraoptic nucleus and the magnocellular regions of the paraventricular nucleus. The local cerebral blood flow rates were surprisingly low in the paraventricular nucleus and the supraoptic nucleus in comparison to the cerebral cortex. Furthermore in these nuclei, the antibody for glucose transporter type-1 revealed two populations of vessels differing by their labelling intensity. The similarities observed between the different nuclei suggest that, in the hypothalamus, all magnocellular regions sense the plasma osmolarity. The low local cerebral blood flow, and the patterns of glucose transporter type-1 labelling and cytochrome oxidase histochemistry suggest that the high vascularization of these hypothalamic nuclei is not related to a high metabolic capacity in basal conditions.

Electronic Resource

1460-9568

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Oxytocin binding sites were detected by autoradiography on films and emulsion-coated sections in the spinal cord of adult and postnatal rats from C8 to L2, using a highly selective 125l-labelled oxytocin antagonist. Oxytocin binding sites were detected on all transverse sections in the dorsal horn, where labelling was scattered over laminae I and II. The autonomic areas, i.e. the intermediolateral cell column, the central grey (lamina X) and the nucleus intercalatus were labelled. Binding in the intermediolateral cell column was most frequently observed on sections from T9 to T11 in adult and T7 to T8 in postnatal rats. In this location, oxytocin binding sites were highly concentrated on cell bodies of putative sympathetic preganglionic neurons; however, not all of these cells were labelled. Diffuse labelling occurred on the dorsal part of the central grey, mainly between T8 and L2. Isolated labelled cells belonging to the nucleus intercalatus were scattered between the central canal and the intermediolateral cell column. In addition, oxytocin binding sites were found on some motoneurons of the lateral group of T12-T13, but only in postnatal rats. The distribution of oxytocin binding sites in the rat spinal cord coincides with that of the oxytocin innervation and strongly suggests a modulatory role of this peptide in sensory and autonomic functions.

Electronic Resource

1432-1246

DNA-adduct ; Effect-markert ; Exposure-markert ; Protein-adductt ; Sensitivity-marker

Springer Online Journal Archives 1860-2000

Medicine

Summary Biologic markers are familiar tools for monitoring human absorption of, and reaction to, potentially toxic chemicals. The concept of applying biologic markers to the risk assessment process is a natural, but more recent, development and the principles remain to be fully elaborated. Biologic markers may be measurements of exposure, of effects, of genetic or induced sensitivity or of disease. The ideal biologic marker for risk assessment purposes is a quantitative measurement of a chemical, biochemical, functional or morphological change in the system that is initiated by a chemical and which results in pathologic change and overt toxicity. It follows that some understanding of the mechanism of toxicity and of dose-response relationships are pre-requisite for selection of suitable biologic markers for use in risk assessment. Where biologic markers for toxicity are common between mammalian species, extrapolation of data for quantitative risk assessment purposes becomes more reasonable. In the field of carcinogenesis, some DNA and protein adducts have been proposed as biologic markers for assessment of risk associated with exposure to genotoxic carcinogens. However, less progress is evident in relation to other toxic end-points including those for pulmonary, reproductive, immuno- and neuro-toxicity, despite intensive efforts.

Electronic Resource

1432-0878

Paraventricular neurones ; Alcian-blue labelling ; Ultrastructure ; Electrophysiology ; Rat

Springer Online Journal Archives 1860-2000

Biology

Medicine

Summary The ultrastructural characterization of electrophysiologically identified neurones of the rat paraventricular hypothalamic nucleus was performed with extracellular labelling technique. The extracellularly recorded neurones are labelled with an electrophoretic deposit of alcian blue contained in the recording micropipette. The neurone thus labelled takes on a dark and shrunken appearance which enables its detection among neighbouring cells without, however, concealing its main morphological characteristics. 1) Spontaneously firing neurones, invaded by an antidromic action potential elicited by electrical stimulation of the neurohypophysis, were identified as magnocellular cells containing dense-cored vesicles of 200–250 nm in diameter. Dense-cored vesicles were not found in the antidromically activated neurones devoid of spontaneous activity. 2) Trans-synaptically activated neurones in the PVN or in its dorso-lateral edge were small cells devoid of dense secretory vesicles. 3) PV neurones in which neurohypophysial stimulation evoked no response, contained small, dense vesicles (100 nm in diameter) comparable with those found in parvocellular peptidergic neurones.

Electronic Resource