J Thibault

Russian Academy of Medical Sciences, Orekhovich Institute of Biomedical Chemistry, Moscow, Moscow, Russia

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Publications (74)183.51 Total impact

  • Article: Degeneration of dopaminergic neurons triggers an expression of individual enzymes of dopamine synthesis in non-dopaminergic neurons of the arcuate nucleus in adult rats.
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    ABSTRACT: Non-dopaminergic neurons expressing individual complementary enzymes dopamine (DA) synthesis were shown to produce DA in cooperation [Ugrumov, M., Melnikova, V., Ershov, P., Balan, I., Calas A., 2002. Tyrosine hydroxylase- and/or aromatic L-amino acid decarboxylase-expressing neurons in the rat arcuate nucleus: ontogenesis and functional significance. Psychoneuroendocrinology 27, 533-548; Ugrumov, M.V., Melnikova, V.I., Lavrentyeva, A.V., Kudrin, V.S., Rayevsky, K.S., 2004. Dopamine synthesis by non-dopaminergic neurons expressing individual complementary enzymes of the dopamine synthetic pathway in the arcuate nucleus of fetal rats. Neuroscience 124, 629-635]. This study was aimed at testing our hypothesis that the cooperative synthesis of DA in non-dopaminergic neurons is an adaptive reaction under functional insufficiency of the dopaminergic system. Functional insufficiency of the tuberoinfundibular dopaminergic system was provoked by 6-OHDA-induced degeneration of dopaminergic neurons in the arcuate nucleus in adult rats. Bienzymatic (dopaminergic) neurons and monoenzymatic neurons expressing tyrosine hydroxylase (TH) or aromatic L-amino acid decarboxylase (AADC) were detected with a double-immunofluorescent technique on cryostat sections. The 6-OHDA-induced degeneration of dopaminergic neurons was accompanied by a significant increase of the number of monoenzymatic TH neurons and AADC neurons that appears to support our hypothesis. The reaction of bienzymatic and monoenzymatic neuron populations to the 6-OHDA administration occurred to be region-specific. The former disappeared in the dorsomedial region of the arcuate nucleus while the latter increased in the ventrolateral region. Thus, degeneration of dopaminergic neurons in the arcuate nucleus of adult rats is accompanied by the expression of individual enzymes of DA synthesis in non-dopaminergic neurons that may be an adaptive reaction.
    Journal of Chemical Neuroanatomy 08/2005; 30(1):27-33. · 2.43 Impact Factor
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    Article: Tyrosine hydroxylase expression in differentiating neurons of the rat arcuate nucleus: stimulatory influence of serotonin afferents.
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    ABSTRACT: The influence of serotonin afferents on tyrosine hydroxylase expression in differentiating neurons of the rat arcuate nucleus was studied in vivo and in vitro. In the in vivo study, pchlorophenylalanine inhibited serotonin synthesis in fetal brain from the 11th to the 20th embryonic day. We then used semiquantitative immunocytochemistry to evaluate tyrosine hydroxylase levels in neurons of the arcuate nucleus in fetuses at the 21st embryonic day or in offspring at the 35th postnatal day. Serotonin depletion significantly decreased the tyrosine hydroxylase content in neurons of males and females at the 21st embryonic day and in males at the 35th postnatal day. For the in vitro study, embryonic neurons of the arcuate nucleus were cocultured with embryonic neurons of the raphe nucleus, the main source of serotonin innervation of the brain, including the arcuate nucleus. Co-culture of the neurons resulted in a gender-specific increase of the tyrosine hydroxylase level in the neurons of the arcuate nucleus. In turn, the neurons of the raphe nucleus showed increased levels of serotonin in both males and females, with no sexual dimorphism. Thus, our results suggest a stimulatory, long-lasting effect of serotonin afferents on tyrosine hydroxylase expression in the differentiating neurons of the rat arcuate nucleus during prenatal ontogenesis.
    Neural plasticity. 02/2001; 8(4):271-84.
  • Article: Tyrosine hydroxylase-expressing and/or aromatic L-amino acid decarboxylase-expressing neurons in the mediobasal hypothalamus of perinatal rats: differentiation and sexual dimorphism.
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    ABSTRACT: In this quantitative and semiquantitative immunocytochemical study, the authors evaluated the differentiation of neurons expressing tyrosine hydroxylase (TH) and/or aromatic L-amino acid decarboxylase (AADC) in the mediobasal hypothalamus (MBH) of male and female rats on embryonic day 18 (E18), E20, and postnatal day 9 (P9). Four neuronal populations were distinguished according to either enzyme expression or neuron location. The earliest and most prominent first population was represented by TH-immunoreactive (IR)/AADC-immunonegative (IN) neurons that were detected initially at E18 and always were located in the ventrolateral region of the MBH. The second population of TH-IN/AADC-IR neurons was observed first at E20 and, after that time, was distributed dorsomedially. The third minor population of TH-IR/AADC-IR neurons initially was detected at E20 and was located dorsomedially. The fourth population was represented by TH-IR/AADC-IN neurons that were distributed in the dorsomedial region at any studied age. The numbers of TH-IR and AADC-IR neurons increased from their initial detection at E18 and E20 until P9. The area of TH-IR and AADC-IR neurons also increased from E18 to E20 and from E20 to P9, respectively. Both TH-IR and AADC-IR neurons showed sex differences in the neuron number, size, and optic density (OD). The numbers of TH-IR neurons in males exceeded those of females at E20 and at P9, although, at P9, sexual dimorphism was a characteristic only of the ventrolateral population. The area and OD of TH-IR neurons from females exceeded those from males in the entire mediobasal hypothalamus (MBH) at E18 and E20 but only in its dorsomedial region at P9. Sexual dimorphism also was an attribute of AADC-IR neurons at E20 and P9. Their number, size, and OD were significantly higher in females than in males. Thus, the MBH of perinatal rats contained two major populations of TH-IR/AADC-IN or TH-IN-AADC-IR neurons and a minor population of TH-IR/AADC-IR neurons. The differentiating neurons expressing either enzyme showed sexual dimorphism.
    The Journal of Comparative Neurology 10/2000; 425(2):167-76. · 3.81 Impact Factor
  • Article: Neuronal projections to the lateral retrochiasmatic area of sheep with special reference to catecholaminergic afferents: immunohistochemical and retrograde tract-tracing studies.
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    ABSTRACT: The retrochiasmatic area contains the A15 catecholaminergic group and numerous monoaminergic afferents whose discrete cell origins are unknown in sheep. Using tract-tracing methods with a specific retrograde fluorescent tracer, fluorogold, we examined the cells of origin of afferents to the retrochiasmatic area in sheep. The retrogradely labeled cells were seen by observation of the tracer by direct fluorescence or by immunohistochemistry with specific antibodies raised in rabbits or horses. Among the retrogradely labeled neurons, double immunohistochemistry for tyrosine hydroxylase, dopamine-beta-hydroxylase, and serotonin were used to characterize catecholamine and serotonin FG labeled neurons. The retrochiasmatic area, which included the A15 dopaminergic group and the accessory supraoptic nucleus (SON), received major inputs from the lateral septum (LS), the bed nucleus of the stria terminalis (BNST), the thalamic paraventricular nucleus, hypothalamic paraventricular and supraoptic nuclei, the perimamillary area, the amygdala, the ventral part of the hippocampus and the parabrachial nucleus (PBN). Further, numerous scattered retrogradely labeled neurons were observed in the preoptic area, the ventromedial part of the hypothalamus. the periventricular area, the periaqueductal central gray (CG), the ventrolateral medulla and the dorsal vagal complex. Most of the noradrenergic afferents came from the ventro-lateral medulla (Al group), and only a few from the locus coeruleus complex (A6/A7 groups). A few dopaminergic neurons retrogradely labeled with flurogold were observed in the periventricular area of the hypothalamus. Rare serotoninergic fluorogold labeled neurons belonged to the dorsal raphe nucleus. Most of these afferents came from both sides of the brain, except for hypothalamic supraoptic and paraventricular nuclei. In the light of these anatomical data, we compared our results with data obtained from rats, and we discussed the putative role of these afferents in sheep in the regulation of several specific functions in which the retrochiasmatic area may be involved, such as reproduction.
    Journal of Chemical Neuroanatomy 06/2000; 19(1):47-67. · 2.43 Impact Factor
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    Article: Tyrosine hydroxylase in vasopressinergic axons of the pituitary posterior lobe of rats under salt-loading as a manifestation of neurochemical plasticity.
    M Abramova, A Calas, J Thibault, M Ugrumov
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    ABSTRACT: In this study, we attempted to test whether tyrosine hydroxylase (TH), the first rate-limiting enzyme of catecholamine synthesis, is confined to the perikarya of activated magnocellular vasopressinergic (VPergic) neurons or is also present in their distal axons in the pituitary posterior lobe (PL). In addition, we evaluated the possible correlation between TH and VP turnover in the axons of rats drinking 2% NaCl for 1, 2, and 3 weeks. To this aim, we examined the large swellings of VPergic axons, the so-called Herring bodies, using the double-immunofluorescent technique and the avidinbiotin technique, combined with image analysis. Here we have demonstrated for the first time a colocalization of TH and VP in Herring bodies, which is a strong argument in favor of TH transport from the perikarya of VPergic neurons via axons toward their terminals. TH-immunoreactive (IR) and VP-IR materials were distributed in Herring bodies with seeming zonality. The number of VP-IR Herring bodies decreased by a factor of four over the first week of osmotic stimulation, remaining at almost the same low level until the end of the experiment. Conversely, the content of the VP-IR material within the individual Herring bodies fell gradually during the three weeks of salt-loading. The results suggest that VP depletion from Herring bodies prevails in its transport into these structures during the whole period of osmotic stimulation. In contrast to VP-IR Herring bodies, the number of TH-IR Herring bodies and the content of TH-IR material within the individual Herring bodies increased progressively during the entire experiment. The synchronization of the VP depletion and TH accumulation in Herring bodies during long-term osmotic stimulation raised the question about a possible functional interaction between both substances.
    Neural plasticity. 02/2000; 7(3):179-91.
  • Article: Structure modelling and site-directed mutagenesis of the rat aromatic L-amino acid pyridoxal 5'-phosphate-dependent decarboxylase: a functional study.
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    ABSTRACT: The pyridoxal-5'-phosphate-dependent enzymes (B6 enzymes) are grouped into three main families named alpha, beta, and gamma. Proteins in the alpha and gamma families share the same fold and might be distantly related, while those in the beta family exhibit specific structural features. The rat aromatic L-amino acid decarboxylase (AADC; EC(4.1.1.28)) catalyzes the synthesis of two important neurotransmitters: dopamine and serotonin. It binds the cofactor pyridoxal-5'-phosphate and belongs to the alpha family. Despite the low level of sequence identity (approximately 10%) shared by the rat AADC and the sequences of the enzymes belonging to the B6 enzymes family, including the known three-dimensional structures, a multiple sequence alignment was deduced. A model was built using segments belonging to seven of the eleven known structures. By homology, and based on knowledge of the biochemistry of the aspartate aminotransferase, structurally and functionally important residues were identified in the rat AADC. Site-directed mutagenesis of the conserved residues D271, T246, and C311 was carried out in order to confirm our predictions and highlight their functional role. Mutation of D271A and D271N resulted in complete loss of enzyme activity, while the D271E mutant exhibited 2% of the wild-type activity. Substitution of T246A resulted in 5% of the wild-type activity while the C311A mutant conserved 42% of the wild-type activity. A functional model of the AADC is discussed in view of the structural model and the complementary mutagenesis and labelling studies.
    Proteins Structure Function and Bioinformatics 12/1999; 37(2):191-203. · 3.39 Impact Factor
  • Article: [Colocalization of vasopressin and tyrosine hydroxyl in axons of the r at hypophysial posterior lobe].
    Doklady Akademii nauk / [Rossiĭskaia akademii nauk] 10/1999; 368(2):268-9.
  • Article: [Response of vasopressin and tyrosine hydroxylase expressing neurons of the rat supraoptic nucleus to chronic osmotic stimulation].
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    ABSTRACT: This study has evaluated the dynamic of intracellular vasopressin and tyrosine hydroxylase contents in the neuron cell bodies in the supraoptic nucleus and in the axons of the posterior lobe in rats drinking 2% NaCl for 1, 2, and 3 weeks. The number of vasopressin-immunoreactive neurons increased by the end of the second week of osmotic stimulation that might be explained by the onset of vasopressin synthesis in the neurons which do not synthesize this neurohormone under normal physiological conditions. The concentration of vasopressin fell down continuously during the first two weeks of salt-loading, apparently, due to predominance of the vasopressin release over its synthesis. Over the third week of salt-loading, the intracellular concentration of vasopressin was not changed significantly suggesting the establishment of the dynamic equilibrium between the vasopressin synthesis and release. The number of tyrosine hydroxylase-immunoreactive neurons and the amount of tyrosine hydroxylase in cell bodies and the large axonal swellings, Herring bodies, increased gradually showing that the rate of tyrosine hydroxylase synthesis prevailed over that of its enzymatic degradation. Thus, the chronic stimulation of vasopressin neurons is accompanied by a number of the adaptive reactions; the most important is related to the onset of vasopressin and tyrosine hydroxylase synthesis in the neurons which do not synthetize both of them under normal conditions.
    Rossiĭskii fiziologicheskiĭ zhurnal imeni I.M. Sechenova / Rossiĭskaia akademiia nauk 07/1999; 85(6):826-34.
  • Article: Afferents to the rostral olfactory bulb in sheep with special emphasis on the cholinergic, noradrenergic and serotonergic connections.
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    ABSTRACT: The olfactory bulb (OB) is involved in the processing of olfactory information particularly through the activation of its afferents. To localize their cell origin in sheep, a specific retrograde fluorescent tracer, Fluoro-Gold, was injected into the olfactory bulb of seven ewes. By using immunocytochemical techniques, retrogradely labeled neurons were colocalized with choline acetyltransferase, tyrosine hydroxylase, dopamine-beta-hydroxylase and serotonin to characterize cholinergic, noradrenergic and serotonergic Fluoro-Gold-labeled neurons. Most afferents originated from the ipsilateral side of the injection site. The OB received major inputs from the anterior olfactory nucleus (AON), the piriform cortex (PC), the olfactory tubercle, the diagonal band of Broca (DBB) and the amygdala. Other retrogradely labeled neurons were observed in the taenia tecta, the septum, the nucleus of the lateral olfactory tract, the preoptic area, the lateral hypothalamic area, the mediobasal hypothalamus, the lateral part of the premammillary nucleus, the paraventricular nucleus of the hypothalamus, the paraventricular thalamic nucleus, the central grey, the substantia nigra (SN), the ventral tegmental area (VTA), the lateral nucleus to the interpeduncular nucleus (IIP), the raphe and the locus coeruleus (LC). Contralateral labeling was also found in the AON, the PC, the SN compacta, the VTA, the IIP and the LC. Cholinergic Fluoro-Gold-labeled neurons belonged to the horizontal and vertical branch of the DBB. Noradrenergic afferents came from the LC and serotoninergic afferents came from the medial raphe nuclei and the 1IP. These data are discussed in relation with olfactory learning in the context of maternal behavior in sheep.
    Journal of Chemical Neuroanatomy 07/1999; 16(4):245-63. · 2.43 Impact Factor
  • Article: Presence of galanin in dopaminergic neurons of the sheep infundibular nucleus: a double staining immunohistochemical study.
    E Chaillou, G Tramu, J Thibault, Y Tillet
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    ABSTRACT: The distribution of tyrosine hydroxylase (TH) and of galanin immunoreactive (IR) neurons were examined in the sheep infundibular nucleus. Antisera raised against TH and galanin were used on adjacent sections and for double immunohistochemical staining of the same sections. There was considerable overlap in the distribution of TH and galanin-IR neurons in the medial part of the nucleus. Most of the galanin-IR neurons were also TH-IR, but less than 50% of the TH-IR neurons also expressed galanin immunoreactivity. Neurons immunoreactive to TH alone were observed close to the third ventricle and in the rostral part of the infundibular nucleus. In the median eminence, TH and galanin-IR fibres overlapped mainly in the lateral and dorsal parts of the external layer, but the colocalisation of both antigens could not be assessed on the available material. Thus, in sheep, the population of catecholaminergic neurons of the infundibular nucleus may be subdivided into different subpopulations according to their peptide content, but does not appear segregated as in rat and human.
    Journal of Chemical Neuroanatomy 11/1998; 15(4):251-9. · 2.43 Impact Factor
  • Article: Immunolocalization of aromatic L-amino acid decarboxylase, tyrosine hydroxylase, dopamine, and serotonin in the forebrain of Ambystoma mexicanum.
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    ABSTRACT: To improve basic knowledge about the neurochemical organization of the urodele brain, and to study discrepancies in the localization of monoaminergic markers, we immunohistochemically charted the distribution of four such markers (tyrosine hydroxylase, aromatic L-amino acid decarboxylase, dopamine, and serotonin) in the axolotl (Ambystoma mexicanum) forebrain. Catecholaminergic and serotoninergic systems were found in similar locations to those seen in other Urodela. As seen in other vertebrates, the localization of the different monoaminergic markers reveals some inconsistencies. Cells that are exclusively tyrosine hydroxylase-immunoreactive are observed in the olfactory bulb, anterior olfactory nucleus/nucleus accumbens region, the epichiasmatic portion of the preoptic nucleus, and in the pars intercalaris thalami, whereas cells that are only labelled by aromatic L-amino acid decarboxylase are seen in the anterior olfactory nucleus/nucleus accumbens region, the bed nuclei of the anterior commissure, the posterior portion of the preoptic nucleus, the ventral hypothalamus, and the pars intercalaris thalami. The presence of cells solely serotonin (5-HT)-immunoreactive is suggested for the nucleus infundibularis dorsalis. Conversely, there were no areas that appeared to be exclusively immunoreactive for dopamine. Double-labelling for aromatic L-amino acid decarboxylase/tyrosine hydroxylase and aromatic L-amino acid decarboxylase/serotonin, together with cell counting, confirmed the existence of neurons that express only one monoaminergic marker in amphibian, supporting the hypothesis that these cells are universally present in the central nervous system of vertebrates.
    The Journal of Comparative Neurology 03/1998; 391(2):227-47. · 3.81 Impact Factor
  • Article: Expression, purification, and characterization of rat aromatic L-amino acid decarboxylase in Escherichia coli.
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    ABSTRACT: A cDNA encoding rat aromatic L-amino acid decarboxylase (AADC) was successfully expressed in Escherichia coli using a T7 RNA polymerase expression system. Two types of expression vectors were tested and revealed to be equivalent to produce AADC. The enzyme was purified in both cases. The ratio of recovery of the pure active recombinant protein was better when the purification of the protein was made easier by addition of a short His-Tag at the C-terminal moiety of AADC, as achieved in the case of pET-20b+ vector expression. Spectral characteristics of the bound pyridoxal-5'-phosphate were essentially identical to the spectral properties of rat AADC. Kinetic constants Km and Vmax of recombinant AADC for the natural substrates L-dihydroxyphenylalanine and 5-hydroxytryptamine were 0.14 mM and 8444 U/mg, and 0.066 mM and 1813 U/mg, respectively. These values were in good agreement with previously reported values for AADC of the rat and other mammalian species.
    Protein Expression and Purification 12/1997; 11(2):185-94. · 1.59 Impact Factor
  • Article: Long-lasting effect of catecholamine deficiency on differentiating vasopressin and oxytocin neurons in the rat supraoptic nucleus.
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    ABSTRACT: According to our earlier study, the catecholamine depletion in neonatal rats resulted in stimulation of the vasopressin and oxytocin gene expression in the neurons of the supraoptic nucleus. The present study extends this line, evaluating whether the catecholamine deficiency provides a long-lasting effect on the differentiating vasopressin and oxytocin neurons of the supraoptic nucleus. Catecholamines were depleted by daily injections of an inhibitor of the catecholamine synthesis, alpha-methyl-p-tyrosine, first, to pregnant rats from the 9th to the 21st day of gestation and, then, to their pups from the 2nd to the 10th postnatal day. The animals, injected with saline instead of drugs, served as controls. The pharmacologically-treated and control rats were kept for four months under normal laboratory conditions until processing the materials for semi-quantitative in situ hybridization and immunocytochemistry of vasopressin and oxytocin messenger RNAs and peptides, respectively. There were no differences in the vasopressin and oxytocin messenger RNA concentrations in the supraoptic nucleus in rats following preliminary catecholamine depletion compared to controls. Conversely, the catecholamine deficiency resulted in an increased content of the vasopressin-immunoreactive material in cell bodies and processes. This was also the case for the oxytocin-immunoreactive cell bodies but only in females, suggesting an interference of catecholamines with sexual steroids in their action. The number and size of vasopressin and oxytocin neurons did not change in pharmacologically-treated rats compared to the controls. Thus, the catecholamine deficiency in the course of the neuron differentiation resulted in a long-lasting augmentation of the intracellular content of vasopressin and oxytocin but did not influence the vasopressin and oxytocin gene expression. This might be explained rather by the reduced level of peptide release than by an increased level of the peptide production.
    Neuroscience 08/1997; 79(2):555-61. · 3.38 Impact Factor
  • Article: Active rat aromatic-L-amino acid decarboxylase as a fusion protein in Escherichia coli.
    F Jebai, J Thibault, M Krieger
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    ABSTRACT: The DNA sequence encoding rat aromatic-L-amino acid decarboxylase (AADC) was inserted into the Escherichia coli (E. coli) expression vector pMAL-c2. This clone produced a fusion protein able to catalyze the conversion of L-DOPA to dopamine. After purification and treatment of the fusion protein by factor Xa (FXa), an enzymatically active form of the enzyme resistant to FXa was isolated. It showed kinetic constants, Vmax, K(m) and enzymatic properties very similar to those obtained previously for the mammalian enzyme. This method for obtaining active AADC appears to be useful for initiating the study of the catalytic activity of this protein because it permitted the rapid isolation and the stabilization of an active form of the enzyme.
    Comptes Rendus de l Académie des Sciences - Series III - Sciences de la Vie 06/1997; 320(5):349-58.
  • Article: Isolation and characterization of ovine tyrosine hydroxylase mRNA.
    Y Tillet, M Krieger, J Thibault
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    ABSTRACT: Tyrosine hydroxylase (TH) cDNA has been characterized in rodents and primates, but only a few studies have been developed in ungulates, except in cows. Because sheep is a species used for many physiological studies, it was of interest to clone TH cDNA in this species. Ovine TH cDNA was purified from a library of sheep adrenal glands. The entire cDNA was 1,721 bp long. It presented a higher percentage of similarity with bovine TH cDNA (93%) than with rodent cDNAs (75%). The deduced amino acid sequence was 490 amino acids long and had 96% similarity with the bovine amino acid sequence. The entire cDNA and different fragments obtained with endonuclease restriction enzymes were cloned in plasmid pUC 18 and were labeled with 35S-dATP to detect TH mRNA by in situ hybridization. Strong labelings were observed on adrenal medulla and on noradrenergic and dopaminergic neurons in the sheep but also in the cow and pig. This labeling matched completely TH immunohistochemical staining obtained on the same sections with anti-TH antibodies. Ovine TH cDNA is a useful tool to study the variations of TH mRNA levels in sheep catecholaminergic neurons.
    Journal of Neurochemistry 06/1997; 68(5):2161-9. · 4.06 Impact Factor
  • Article: Characterization of the short day-induced decrease in median eminence tyrosine hydroxylase activity in the ewe: temporal relationship to the changes in luteinizing hormone and prolactin secretion and short day-like effect of melatonin.
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    ABSTRACT: In the ewe, photoperiod modulates LH and PRL secretion as well as median eminence (ME) dopaminergic activity. The studies reported here were designed to characterize the functional significance of this photoperiodic modulation of ME dopaminergic neuron activity in relation to the regulation of LH and PRL secretion. The aim of the first experiment was to assess whether photoperiodic changes in hypothalamic dopaminergic activity were temporally linked to changes in either PRL or LH secretion. The purpose of the second experiment was to determine whether melatonin mimicked the effects of photoperiod on ME dopaminergic activity. In the first experiment, LH and PRL secretion, hypothalamic tyrosine hydroxylase (TH) activity, and catecholamine contents were determined in ovariectomized estradiol-treated ewes either during long days (LD; control group) or after 5, 25, and 76 short days (SD). SD were associated with a stimulation of LH secretion and a decrease in ME TH activity, which were both expressed only in the 76 SD group. In contrast, the SD-induced inhibition of PRL secretion was already maximal in the 25 SD group. In the second experiment, LH secretion and hypothalamic dopaminergic activity were studied in ovariectomized estradiol-treated ewes kept in LD and then treated for 0 (control), 25, or 77 days with melatonin implants producing a SD-like effect on LH secretion. Melatonin induced a decrease in PRL secretion (observed after 25 days of treatment), as well as a stimulation of LH secretion and a decrease in ME TH activity and dopamine content (observed only after 77 days of treatment). In conclusion, the decrease in ME dopaminergic activity associated with SD exposure or the SD-like effect of melatonin appears unrelated to the regulation of PRL secretion. The SD-like effect of melatonin on ME dopaminergic activity suggests that melatonin mediates the effect of SD on this activity. The regulation of ME dopaminergic activity can thus be considered a probable step in the photoperiodic regulation of LH secretion.
    Endocrinology 02/1997; 138(1):499-506. · 4.46 Impact Factor
  • Article: Birthdates of the tyrosine hydroxylase immunoreactive neurons in the hypothalamus of male and female rats.
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    ABSTRACT: This study determined the birthdates of the tyrosine hydroxylase-(TH) immunoreactive (IR) neurons in the zona incerta (ZI), periventricular nucleus (PeVN) and arcuate nucleus (AN) of male and female rats. 'Long-survival' [3H]thymidine autoradiography combined with TH immunocytochemistry, the first enzyme of catecholamine synthesis, was used. In males, TH-IR neurons originate in the ZI between embryonic days (E) 12 and 13, while in the PeVN and AN this process is prolonged until E16. The majority of TH-IR neurons became postmitotic at E12 in the ZI, between E12 and E14 in the PeVN and at E15 in the AN. The birthdate of TH-IR neurons was sexually dimorphic with (a) generation of the majority of TH-IR neurons in the ZI in males proceeding that in females, (b) generation of TH-IR neurons in the AN of males delayed as compared to females, and (c) average daily fractions of the newborn TH-IR neurons in each hypothalamic region of females exceeding that seen in males. This sexual dimorphism was observed prior to E16, i.e. before the onset of sex difference in androgen levels, implying a hormone-independent mechanism, determined at the genetic level.
    Neuroendocrinology 01/1997; 64(6):405-11. · 2.38 Impact Factor
  • Article: Photoperiodic modulation of monoamines and amino-acids involved in the control of prolactin and LH secretion in the ewe: evidence for a regulation of tyrosine hydroxylase activity.
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    ABSTRACT: Several neurotransmitters are implicated in the photoperiodic regulation of prolactin and luteinising hormone (LH) secretion in the ewe. This work investigated whether catecholamines, gamma-amino butyric acid (GABA), excitatory amino acids and serotonin diencephalic contents are affected by photoperiod and how such changes relate to the seasonal effects of photoperiod on LH and prolactin secretions. Moreover, to determine whether photoperiod can influence catecholamine biosynthesis, the activity of its rate limiting enzyme, tyrosine hydroxylase (TH) was also investigated. TH activity and the tissue content of the monoamines and their metabolites were measured in stalk-median eminence (SME), preoptic area (POA) and the mediobasal, mediodorsal and laterobasal aspects of the hypothalamus. Investigation of excitatory amino acids and GABA was limited to the POA and the SME. Ovariectomized ewes were initially maintained in long days (LD) for 70 days. Thereafter half the ewes remained exposed to long days and the other half were transferred onto short days (SD) for 63 to 66 days to induce a stimulation of LH secretion and an inhibition of prolactin secretion. In each photoperiodic regime, half the ewes were treated with a subcutaneous oestradiol implant (+E) and half were not (-E). As expected, short days induced a decrease in prolactin and an increase in pulsatile LH secretion. These neuroendocrine changes were associated with a decrease in the TH activity of the SME in both oestradiol treated and non treated animals (146.5 +/- 24.1, 167.6 +/- 26.5 U TH/g of tissue in LD-E and LD+E vs 83.5 +/- 12.4 and 95.0 +/- 30.2 U TH/g of tissue in SD-E and SD+E animals; P < or = 0.01). A similar and parallel short day-induced decrease was observed in the tissue content of dopamine and its metabolite, 3,4-dihydroxy-phenylacetic acid (SD level were 55% of LD levels, P < 0.05). In POA, a short day-induced decrease in dopamine (18%; P < or = 0.05) and GABA (16.4%; P < or = 0.05) content and an oestradiol-induced decrease in aspartate (15.6%; P < or = 0.05) content were found. This study provides the first report of a photoperiodic control of the synthesis activity of catecholaminergic neurones of the SME in the ewe. The photoperiod-induced changes in dopaminergic activity at the level of the SME were associated with changes in LH and prolactin secretion indicating that TH activity of dopaminergic neurones of the SME could be a critical component of the photoperiodic regulation of LH and/or prolactin secretion. In particular, this finding is in agreement with the hypothesis that photoperiod can control a dopaminergic pathway inhibitory of LH secretion and which ends in the median eminence.
    Journal of Neuroendocrinology 06/1996; 8(6):465-74. · 3.14 Impact Factor
  • Article: Chromosomal localization of the human and mouse histidine decarboxylase genes by in situ hybridization. Exclusion of the HDC gene from the Prader-Willi syndrome region.
    P Malzac, M G Mattei, J Thibault, G Bruneau
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    ABSTRACT: Using a rat histidine decarboxylase (HDC) cDNA probe, we have mapped the HDC gene by in situ hybridization to the q15-q21 region of human chromosome 15 and to the E5-G region of murine chromosome 2. These localizations strengthen a syntenic group conserved between human chromosome 15 and mouse chromosome 2. The localization of the HDC gene on the human chromosome 15 map shows that it is not included within the Prader-Willi Syndrome region (PWCR).
    Human Genetics 04/1996; 97(3):359-61. · 5.07 Impact Factor
  • Article: A confocal approach to the morphofunctional characterization of the transient tyrosine hydroxylase system in the rat suprachiasmatic nucleus.
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    ABSTRACT: The suprachiasmatic nucleus (SCN) of the neonatal rat is transiently innervated by tyrosine hydroxylase (TH) fibers of unknown origin and whose catecholaminergic nature is rather doubtful. In order to characterize this system morphofunctionally, immunocytochemical double labelling and confocal laser scanning microscopy analysis were employed on cryostat brain sections of 10-day-old rats. Simultaneous stainings for neuropeptide Y (NPY) and tyrosine hydroxylase (TH) immunoreactivity showed that they are not colocalized, neither in the SCN fibers nor in the intergeniculate leaflet (IGL) neurons, site of origin of the NPY projection to the SCN. Therefore, the possibility that SCN transient TH fiber system originates from the IGL could be excluded. Double labelling for TH and aromatic L-aminoacid decarboxylase (AADC) demonstrated that transient SCN TH immunoreactive (IR) fibers are AADC negative, thus supporting the hypothesis of their non-catecholaminergic nature. Moreover two new group of cells which are TH positive and AADC negative were found: one in the SCN and the other in the periventricular hypothalamic nucleus (PHN). The presence of somatostatin (SRIF) and TH in PHN neurons and SCN fibers suggested their possible colocalization, but double immunolabellings gave negative results. Simultaneous immunocytochemical staining for vasoactive intestinal polypeptide (VIP) and TH showed that TH fibers may interact with ventrolateral SCN VIP neurons. This result suggests a possible involvement of TH fibers in regulating VIP cells activity in the entrainment of circadian rhythms.
    Brain Research 11/1995; 696(1-2):7-14. · 2.73 Impact Factor

Institutions

  • 2000–2005
    • Russian Academy of Medical Sciences, Orekhovich Institute of Biomedical Chemistry
      Moscow, Moscow, Russia
  • 1989–2001
    • Russian Academy of Sciences
      • • Institute of Developmental Biology
      • • Laboratory of Hormonal Regulations
      Moscow, Moscow, Russia
  • 1994–2000
    • French National Institute for Agricultural Research
      • Physiologie de la Reproduction et des Comportements (PRC)
      Paris, Ile-de-France, France
  • 1988–1999
    • French National Centre for Scientific Research
      Lyon, Rhone-Alpes, France
  • 1986–1997
    • Collège de France
      Paris, Ile-de-France, France
  • 1984–1997
    • Université Pierre et Marie Curie Paris 6
      Paris, Ile-de-France, France
  • 1992
    • University of Bergen
      Bergen, Hordaland Fylke, Norway