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Biomedical subjects

M Fevre-Montange

Publications and source records attributed to M Fevre-Montange.

10 recordsLinked to original sources

Somatotopic organization of tyrosine hydroxylase expression in the rat locus coeruleus: long term effect of RU24722.

Tyrosine hydroxylase (TH) tissue concentration was determined by immunostaining of tissue sections directly transferred onto nitrocellulose membranes in the restricted region of the noradrenergic perikarya of the locus coeruleus (LC) along its postero-anterior axis. TH containing cells were systematically counted on adjacent post fixed sections stained by immunohistochemistry. The absolute quantity of TH was estimated in each section and was found to be linearly related to the number of TH immuno-positive cells found in the adjacent section. The ratio between these two parameters was thus used as an index of the cellular concentration of TH in noradrenergic cells. In the LC of control rats, the TH cellular concentration was lower (-39%) in the anterior than in the posterior half of the structure. Three days after an injection of 20 mg/kg of RU24722, an eburnamine derivative known to increase the quantity of TH in the LC, increases in quantities of TH were found in both portions of the LC. Moreover in the posterior LC the increase in the amount of TH resulted from a significant increase in the number of TH-immunopositive cells. In the anterior part, however, it was primarily the result of a significant increase in TH cellular concentration. Throughout the LC there was an increase in the cellular concentration of TH which was inversely proportional to the concentrations found in control animals. TH mRNA content was measured by a quantitative in situ hybridization in sections of both the posterior and anterior LC one day after a single injection of RU24722 at the same dose. The quantity of TH mRNA was significantly increased in both parts. The number of TH mRNA-expressing neurons also increased, especially in the anterior LC. Thus the effects at the level of TH protein and TH mRNA were strikingly parallel though increase in TH protein occurred later than the increase in the TH mRNA. These results suggest that in the rat LC: (1) there is a significant population of 'sleeping cells' in which TH expression is either inactivated or, at a low level of activation; (2) TH cellular concentration could exert a retrocontrol on its own expression in cells of the LC that contained TH and (3) TH expression appears to be regulated by different selective mechanisms in these two different subpopulations of noradrenergic cells within the LC.

Animals

[Demonstration of prolactin messenger RNA after amplification in the brain in rats].

By means of immunocytochemistry, a central neuronal network containing a prolactin-like substance has been described in the rat. In order to demonstrate the synthesis of this peptide in these cells, we examined the presence of prolactin messenger RNA (PRL mRNA) in several brain samples including the pituitary gland. Amplification of the PRL mRNA was performed by the polymerase chain reaction technique, followed by southern blotting and hybridization with a specific oligonucleotide. Results showed the presence of the expected cDNA (468 bp) in the hypothalamus. Another cDNA with a lower molecular weight was also observed.

Animals

Primary dissociated cell culture of embryonic rat metencephalon: presence of GABA in serotonergic neurons.

This study was performed to determine whether neurons, where gamma-aminobutyric acid (GABA) and serotonin (5-HT) coexist, represent neuronal entities which can survive in vitro. In dissociated cultures from 18-day-old embryonic rat metencephalon, it was possible to develop glial and neuronal cells. Among the neurons, some of them, which contain glutamate decarboxylase or are capable of accumulating [3H]GABA are GABAergic; others, containing tryptophan hydroxylase or 5-HT are serotoninergic. By combining radioautography and immunocytochemistry, it was possible to observe neurons where 5-HT and GABA coexist. Cultures might be a suitable model to study the functioning (release or synthesis of both neurotransmitters) of neurons where two classical neurotransmitters coexist.

Animals

Developmental expression of glial markers in ependymocytes of the rat subcommissural organ: role of the environment.

The rat subcommissural organ (SCO), principally composed of modified ependymocytes (a type of glial cell), is a suitable model for the in vivo study of glial differentiation. An immunohistochemical study of the ontogenesis of rat SCO-ependymocytes from embryonic day 13 to postnatal day 10 shows that these cells express transitory glial fibrillary acidic protein (GFAP) from embryonic day 19 until postnatal day 3. However, S100 protein (S100) is never expressed in the SCO-cells, contrasting with the ventricle-lining cells of the third ventricle, which contain S100 as early as embryonic day 17. Environmental factors could be responsible for the repression of GFAP and S100 in adult rats, because GFAP and S100 are observed in ependymocytes of SCO 3 months after being grafted from newborn rat into the fourth ventricle of an adult rat. Neuronal factors might be involved in the control of the expression of S100, since after the destruction of serotonin innervation by neurotoxin at birth, S100 can be observed in some SCO-ependymocytes of adult rats. On the other hand, GFAP expression is apparently not affected by serotonin denervation, suggesting the existence of several factors involved in the differentiation of SCO-cells.

5,7-Dihydroxytryptamine

[Demonstration of viral proteins and RNA in hypothalamus of mice infected by canine distemper virus].

There are a number of reports suggesting that neurological disorders may be due to infectious agents, such as viruses. In order to study the role of viruses on cellular plasticity in the central nervous system, we established a model of virus infection in the mouse. Inoculation of mouse with canine distemper virus (CDV) led to an acute encephalitis, late neurological disorders and an obesity syndrome. To analyse the role of viral replication on the development of this syndrome we studied the cerebral distribution of viral products during the course of infection. Viral proteins and RNA accumulated in mouse brain from the 9th day to the 6th week post-inoculation, particularly in hypothalamus, a cerebral structure implicated in obesity. Such selective viral tropism may explain some of the unexpected features of viral-induced disorders.

Animals

[Ultrastructural localization of mRNA coding for oxytocin by in situ hybridization. Study by high resolution autoradiography using a tritiated oligonucleotide probe].

In situ hybridization (ISH) using a 25 mer tritiated oligonucleotide probe has been performed to study at the electron microscopic level the subcellular localization of the oxytocin mRNA in the rat hypothalamic magnocellular neurons. After high resolution radioautography, silver grains appeared to be localized over the cytoplasm of some magnocellular neurons of the supra-optic nucleus and frequently overlapped the ergastoplasmic "cisternae" of the Nissl bodies. These results demonstrate the possible application of ISH at a subcellular level using high resolution radioautography and a tritiated probe.

Animals

Increased luteinizing hormone sensitivity to dopaminergic inhibition in Graves' disease.

The effect of dopamine infusion (4 micrograms X kg-1 X min-1 from 9.00 to 13.00 h) on serum LH and FSH concentrations were studied in 15 patients (10 women, 5 men) with diffuse toxic goitre, and 10 healthy subjects (6 women, 4 men). Basal serum LH (17.0 +/- 0.8 IU/l) and oestradiol (women: 3.74 +/- 1.84; men: 3.05 +/- 0.77 pmol/l) were elevated in patients, whereas serum FSH and PRI were normal. Dopamine infusion did not modify serum FSH levels, but significantly depressed LH concentration in both hyperthyroid and healthy subjects. The LH decrement was more pronounced (P less than 0.01) in patients with Graves' disease (8.4 +/- 1.4 IU/l) as compared with controls (2.3 +/- 0.9 IU/l). There was a positive correlation between the maximum net decrease and the basal LH concentration (r = 0.95). The per cent decrease of LH levels in the hyperthyroid patients (54 +/- 4) was higher (P less than 0.001) than that in the controls. The finding of enhanced sensitivity to dopamine inhibition in thyrotoxic patients suggests that their inappropriately elevated serum LH levels may result in part from a reduced dopaminergic inhibition of LH secretion.

Adult

TRH and LH-RH distribution in discrete nuclei of the human hypothalamus: evidence for a left prominence of TRH.

Thyrotropin-releasing hormone (TRH) and luteinizing hormone-releasing hormone (LH-RH) have been measured by radioimmunoassay in individual human hypothalamic nuclei. A significant lateralization has been found for TRH in the ventromedial, dorsal and paraventricular nuclei, with higher concentration in the left side. In contrast LH-RH values did not differ between the left and the right side. This finding represents an additional example of cerebral specialization and the first report of lateralized peptide distribution in the human hypothalamus.

Adult

The 24-h cortisol secretory pattern in Cushing's syndrome.

The 24-h plasma cortisol profile was obtained at 20-min intervals in 18 patients with Cushing's syndrome (10 with Cushing's disease, 5 with adrenal adenoma, 2 with ectopic ACTH secretion and 1 of questionable aetiology). The mean cortisol level was maximum in the case of ectopic ACTH secretion. The coefficient of variation of cortisol levels was subnormal in all except 2 subjects. Periodogram calculations, providing a best-fit curve (B F C) for each profile, showed that the existence of a significant baseline variation is a frequent feature. In certain cases, it is compatible with the persistence of a true circadian rhythm (2 patients with Cushing's disease; 1 patient with adrenal adenoma). The alteration of plasma cortisol pulsatility is much more pronounced in patients with adrenal adenoma than in patients with Cushing's disease. This is consistent with the hypothesis of a predominantly tonic secretion blunting the episodic hormone release. In 9 patients with Cushing's disease, the plasma cortisol pattern was suggestive of a combination of episodic cortisol release under CRF control and of continuous cortisol secretion due to constant stimulation from an autonomous ACTH source. Two cases were possibly of hypothalamic origin, as suggested by the presence of enhanced cortisol pulsatility and of a normal circadian amplitude. The analysis of the 24-h profile of plasma cortisol in Cushing's syndrome contributes to our understanding of the physiopathological mechanisms underlying this disorder and may help the diagnosis of its aetiology.

Adrenocorticotropic Hormone

[Melatonin].

Melatonin is an indolamine synthesized from tryptophan in the pineal gland. It is regarded as "the epiphyseal hormone". Its antigonadotropic action has been demonstrated in animals, both in vitro and in vivo, together with its inhibitory effect on numerous endocrine functions and its anti-convulsive properties. Recently developed assay methods have made it possible to obtain clinical data, for the moment purely descriptive. Melatonin is present in several body fluids, such as urine, blood and cerebrospinal fluid. It is secreted in circadian cycles, with low concentrations during the day and high concentrations at night; sex has no influence on this pattern, but secretion is highest in the summer and winter and lowest in the spring and autumn. The part played by melatonin in the genesis of puberty is undetermined. Melatonin secretion appears to be mediated by the adrenergic system, since beta-blockers inhibit the nocturnal rise. However, contrary to what happens in animals, most beta-adrenergic stimulants do not increase melatonin concentrations. Abnormal concentrations or perturbations in the melatonin secretion rhythm have been demonstrated in such diseases as breast cancer, cirrhosis of the liver, Klinefelter's syndrome, Cushing's syndrome and haemochromatosis. Depressive syndromes are often associated with abnormal melatonin cycles. It has been suggested that melatonin could be used as a biological marker in cancer and psychiatric diseases, but its physiological function in man remains obscure.

Adolescent