Publications by authors named "Daval G"

As a consequence of the COVID-19 pandemic, the European Society of Cardiology (ESC) was forced to pivot the scientific programme of the ESC Congress 2021 into a totally new format for online consumption, . A variety of new suppliers were involved, including experts in TV studio, cloud infrastructure, online platforms, video management, and online analytics. An information technology platform able to support hundreds of thousands simultaneous connections was built and cloud computing technologies were put in place to help scale up and down the resources needed for the high number of users at peak times.

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Introduction: In some situations such as post-virus or post whooping cough, a non productive subacute cough may occur without apparent local inflammation, epithelium abnormalities or bronchoconstriction. This subacute or chronic cough represents a real syndrome (cough disease) due to the central nervous system (CNS) and its ortho and parasympathic outputs. At the CNS level, functional disturbancies and neosynaptogenesis can be described, with the intervention of the NMDA-type glutamatergic receptors.

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Serotonin (5-HT) plays a major role at the spinal level by modulating most spinal functions through several receptor subtypes including the 5-HT2A receptor. To gain further insight into the cellular role of this receptor, we performed an immunocytochemical study of 5-HT2A receptors in the rat spinal cord, at light and electron microscope levels. The results showed that 5-HT2A receptors were widely distributed in the spinal cord at all segmental levels.

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The distribution of 5-hydroxytryptamine1A and 5-hydroxytryptamine1B receptors in the visual cortex was studied by quantitative autoradiography during postnatal development. Overall, receptor densities increased throughout development, but exhibited regional rearrangements, particularly in the case of 5-hydroxytryptamine1B receptors. Neonatal treatment with 5,7-dihydroxytryptamine, which causes selective degeneration of serotoninergic neurons, had no effect on the density of 5-hydroxytryptamine1A receptors in the visual cortex.

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The possible colocalization of 5-hydroxytryptamine1A receptors and choline acetyltransferase in the same neurons of the medial septum and diagonal band of Broca was investigated using double immunocytochemical techniques, either on the same section or on adjacent thin sections of the rat brain. The presence of both antigens in the same neurons was demonstrated at the light and electron microscopic levels. The proportion of cholinergic neurons that express 5-hydroxytryptamine1A receptors was similar in the different parts of the septal complex (around 25%).

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Modifications in serotonin (5-HT) neurotransmission have been associated with the physiopathology of anxiety and depression. Among the numerous 5-HT receptor subtypes, several (5-HT1A, 5-HT1B, 5-HT2 and 5-HT3) could be involved in these etiologies. By using a murine genetic model, we attempted to correlate variations in the density of receptor subtypes with modifications of anxiety-related behaviors.

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Specific anti-rat 5-hydroxytryptamine1A (serotonin1A) receptor antibodies raised in a rabbit injected with a synthetic peptide corresponding to a highly selective portion of the third intracellular loop of the receptor protein (El Mestikawy et al. [1990] Neurosci. Lett.

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The localization of the rat brain 5-HT1A receptor mRNA was analyzed by RNAse mapping and in situ hybridization during postnatal development, particularly in the cerebellum. The regional distribution of 5-HT1A mRNA during the first 2 postnatal weeks was different from that found in adults. In some areas of the immature brain (hippocampus, cerebral cortex), 5-HT1A mRNA was found in lower density than in the adult brain.

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The serotonin 5-HT1A receptors were visualized in the cerebellar vermis of 8-day-old and adult rats by immunocytochemistry using anti-5-HT1A receptor antibodies raised against a synthetic peptide corresponding to a highly selective portion of the receptor amino acid sequence (El Mestikawy et al, Neurosci Lett 118, 189-192, 1990). The 5-HT1A receptor-like immunoreactivity was particularly abundant in the posterior lobules (IXB-X) of the immature vermis where it was found in the molecular-Purkinje cell layers. Immunostaining was confined to the plasmic membrane of the Purkinje cell somas, dendrites and perhaps axons (at their somatic emergence) suggesting that 5-HT receptors might participate in non-junctional 5-HT neurotransmission in the immature cerebellum.

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5-Hydroxytryptamine1A receptors were studied in rats during the first postnatal month in the normal cerebellum and in the granule cell-deprived cerebellum produced by X-irradiation at postnatal day 5. Quantitative autoradiographic studies on sagittal sections of cerebellar vermis, using [1251]BH-8-MeO-N-PAT as radioligand or specific anti-receptor antibodies, revealed that 5-hydroxytryptamine1A receptors existed in the molecular/Purkinje cell layer but at variable density from one lobule to another. Thus, in both normal and X-irradiated rats, the posterior lobules were more heavily labelled than the anterior ones, and the density of 5-hydroxytryptamine1A sites decreased progressively in all the cerebellar folia down to hardly detectable levels at postnatal day 21.

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Numerous data suggested that the pharmacological and biochemical properties of 5-hydroxytryptamine1A (5-HT1A) receptors exhibit some regional differences in the CNS, notably within the raphe nuclei compared with various forebrain areas (such as the hippocampus). This possibility has been further investigated in the dorsal raphe nucleus and two areas within the hippocampus, the dentate gyrus and the CA1 area, using the quantitative autoradiographic technique. The potencies of 5'-guanylylimidodiphosphate to inhibit the specific binding of 125I-Bolton-Hunter-8-methoxy-2-(N-propyl-N-propylamino)tetralin (125I-BH-8-MeO-N-PAT) to 5-HT1A sites and of N-ethylmaleimide to block these sites irreversibly were identical in the dorsal raphe nucleus and the hippocampal areas in rat brain sections.

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The autoradiographic technique is the most relevant approach for the visualization at the light microscope level of the different classes (5-HT(1A), 5-HT(1B), 5-HT(1C), 5-HT(1D), 5-HT(2) and 5-HT(3)) of receptors for the monoamine neurotransmitter serotonin (5-HT) in the central nervous system of mammals, including man. The only exception is the 5-HT(4) subtype for which no satisfactory radioligand has been developed to date. Quantitative estimates of receptor labelling can be achieved by measurements of optical density on autoradiographic films of brain sections incubated with specific radioligands.

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Polyclonal antibodies were raised by the repeated injection of rabbits with a synthetic peptide corresponding to a highly selective portion (amino acid residues 243 to 268) of the amino acid sequence of the rat 5-HT1A receptor. The anti-peptide antiserum allowed the immunoprecipitation of 5-HT1A receptors but not of other 5-HT1 sites solubilized from rat hippocampal membranes. Immunoautoradiographic labelling of rat brain sections with the anti-peptide antiserum was superimposed with the autoradiographic distribution of 5-HT1A sites labelled by the selective radioligand [3H]8-OH-DPAT.

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Measurements of endogenous levels of serotonin (5-HT), 5-hydroxyindole acetic acid (5-HIAA), dopamine (DA) and dihydroxyphenyl acetic acid (DOPAC), and biochemical and autoradiographic investigations on 5-HT and DA receptors were made in various brain regions in male rats at three different ages: 3 months, 10 months and 22 months. Age-dependent decreases in 5-HT levels associated with parallel increases in 5-HIAA/5-HT ratio were observed in the hypothalamus, striatum, hippocampus and cerebral cortex, suggesting an accelerated 5-HT turnover in aged rats. Similarly, DA levels were lower, and DOPAC/DA ratio was higher in the striatum of 22-month-old compared to 3-month-old or 10-month-old rats.

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The possible irreversible blockade of 5-hydroxytryptamine1 receptor subtypes 5-hydroxytryptamine1A, 5-hydroxytryptamine1B/5-hydroxytryptamine1D and 5-hydroxytryptamine1C by the chloramine 8-methoxy-2-(N-2'-chloropropyl,N-propyl)aminotetralin (8-MeO-2'-chloro-PAT) was investigated in rat brain sections by quantitative autoradiography using [3H]8-hydroxy-2-(di-n-propylamino)tetralin [( 3H]8-OH-DPAT), [3H]5-hydroxytryptamine, [125I]BH-8-MeO-N-PAT and [125I]cyanopindolol as radio-ligands. A marked reduction (-50% to -75%) of [3H]8-OH-DPAT and [125I]BH-8-MeO-N-PAT specific binding to 5-hydroxytryptamine1A sites in the hippocampus (CA1 area) and the dorsal raphe nucleus, and of [3H]5-hydroxytryptamine specific binding to 5-hydroxytryptamine1C sites in the choroid plexus was found in sections exposed to 1 microM 8-MeO-2'-chloro-PAT and then washed extensively. In contrast the specific binding of [3H]5-hydroxytryptamine to 5-hydroxytryptamine1B/5-hydroxytryptamine1D sites and of [125I]cyanopindolol to 5-hydroxytryptamine1B sites in the substantia nigra and dorsal subiculum remained unaltered by this treatment.

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Several classes of 5-HT and dopamine (DA) receptor binding sites, and the levels of 5-HT, 5-hydroxyindoleacetic acid (5-HIAA), DA and dihydroxyphenylacetic acid (DOPAC) were examined in various brain regions 24 h after a 10-day treatment with morphine (2 X 15 mg/kg s.c. daily) in adult rats.

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Article Synopsis
  • In vitro binding assays with a specific radioactive compound showed that it binds effectively to targeted serotonin (5-HT) sites in rat hippocampal membranes.
  • The compound demonstrated high affinity similar to another well-known serotonin agonist, indicating that both interact with the same receptor sites.
  • These findings suggest that the compound is the first reversible ligand for selectively identifying 5-HT1A sites in the rat brain, which is important for understanding serotonin-related functions.
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Specific radioactive ligands are needed for studying the pharmacological properties and the regional distribution of the different classes of 5-HT1 receptors within the central nervous system. We describe here the synthesis and some characteristics of the first iodinated specific ligand of 5-HT1A receptors. Like its parent compound, the agonist 8-hydroxy-2-(di-n-propylamino)tetralin or 8-OH-DPAT, [125I]-BH-8-MeO-N-PAT, exhibits a high affinity and excellent selectivity for 5-HT1A sites.

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Spinal serotonin1 (5-HT1)(labelled by [3H]5-HT), 5-HT1A (labelled by [3H]8-hydroxy-2-(di-n-propylamino)tetralin ([3H]8-OH-DPAT)), mu- (labelled by [3H]Tyr-D-Ala-Gly-(Me)Phe-Gly-ol ([3H]DAGO) and [3H]naloxone) and delta-opiate (labelled by [3H]Tyr-D-Ser-Gly-Phe-Leu-Thr [( 3H]DSTLE] receptor binding sites were studied in adult rats using quantitative autoradiography after either neonatal treatment with capsaicin or unilateral cervical dorsal rhizotomy. Both treatments produced a significant loss of 5-HT (-20 to -30%) and opiate (-30 to -45%) binding sites within the superficial layers of the dorsal horn, suggesting they are partly located presynaptically on primary afferent fibres. Thus, 5-HT, as well as opiates, might generate analgesia by acting--at least partly--on primary afferent nociceptive fibres at the spinal level.

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The developmental evolution of 5-HT1A receptor binding sites was examined in the rat CNS during the early postnatal period using quantitative autoradiography and binding assays with 3H-8-OH-DPAT as the selective ligand. A progressive increase in the density of 5-HT1A sites was observed in the hippocampus, septum and cerebral cortex, up to adult levels which were reached around the third postnatal week. In contrast, complex biphasic (increase then decrease) changes were noted in other structures (for instance the nucleus of the lateral lemniscus), and even a progressive decrease in the density of 5-HT1A sites took place in the cerebellum during the first two postnatal weeks.

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The distribution of the 2 main types (A and B) of 5-HT1 binding sites in the rat brain was studied by light-microscopic quantitative autoradiography. The 5-HT1A sites were identified using 3H-8-hydroxy-2-(N-dipropylamino)tetralin (3H-8-OH-DPAT) or 3H-5-HT as the ligand. In the latter case, it was shown that 3H-5-HT binding to 5-HT1A sites corresponded to that displaceable by 0.

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Neural spike activity was recorded from 50 single mitral cells in the Rabbit olfactory bulb, with variable intensity of the odour stimulation. Six different concentrations were used for two olfactory stimuli, isoamyl acetate and propanol. The discharge frequency of 40 p.

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The responses to odour stimulation of 61 single mitral cells and of 64 single anterior olfactory nucleus (AON) units were simultaneously recorded from rabbits. The test battery consisted of 6 chemical stimuli delivered at two intensity levels corresponding to a hundred-fold difference in concentration. The odour discrimination reaches its best for the mitral cells stimulated weakly; it decreased somewhere when the same cells are stimulated strongly.

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