Brain serotonergic circuitries

Brain serotonergic circuitries interact with other neurotransmitter systems on a multitude of different molecular levels. In humans, as in other mammalian species, serotonin (5-HT) plays a modulatory role in almost every physiological function. Furthermore, serotonergic dysfunction is thought to be implicated in several psychiatric and neurodegenerative disorders. We describe the neuroanatomy and neurochemistry of brain serotonergic circuitries. The contribution of emergent in vivo imaging methods to the regional localization of binding site receptors and certain aspects of their functional connectivity in correlation to behavior is also discussed. 5-HT cell bodies, mainly localized in the raphe nuclei, send axons to almost every brain region. It is argued that the specificity of the local chemocommunication between 5-HT and other neuronal elements mainly depends on mechanisms regulating the extracellular concentration of 5-HT, the diversity of high-affinity membrane receptors, and their specific transduction modalities

Effects of constant infusion with insulin-like growth factor-I (IGF-I) to immature female rats on body weight gain, tissue growth, and sexual function: Evidence that such treatment does not affect sexual maturation or fertility

Plasma levels for insulin-like growth factor-I (IGF-I) steadily increase in female rats between 20 and 40 d of life, and this increase is intimately related to the wellknown growth spurt occurring at this age. Since specific actions of IGF-I related to sexual function have been described at the ovarian and hypothalamic levels, an endocrine role of rising circulating IGF-I levels during sexual maturation cannot be excluded. Therefore, the impact of adult-type plasma IGF-I levels during the juvenile age, on body weight (BW) gain, growth of several organs, sexual development, and fertility has been evaluated. Female Sprague-Dawley rats were infused with rhIGF-I (2 and 4 μg/g BW/d, using Alzet minipumps), between 20 and 41 d of life. When infusing 2 μg/g BW/d, plasma levels for IGF-I were increased 1.5- to 2-fold over controls at all ages studied. They were further increased with the higher dosage, but only after 35 d of age. Plasma levels for insulin-like growth factor binding protein (IGFBP)-1 to-3 were clearly increased. BW gain was significantly increased, but only with the higher dosage. Tail length was never modified. In contrast, a growth acceleration for spleen, kidneys, adrenals, and ovaries was observed with both dosages. The ovarian weight of treated animals represented approx 140% of control animals with the 4 μg/g BW/d dosage. Histology of the enlarged ovaries did not reveal any abnormalities. No meaningful modification of the timing of vaginal opening was observed, and fertility was not compromised by previous rhIGF-I infusion during the 20-41 d age period. In summary, early exposure to increased (adult-like) plasma IGF-I levels did not modify BW gain or tail length, but affected the development of spleen, kidneys, adrenals, and ovaries. Exposure to supraphysiological plasma IGF-I levels (>1200 ng/mL), accelerated BW gain and increased the weight of all organs studied. No signs of precocious sexual maturation were seen and fertility was normal. In conclusion, prematurely increased plasma IGF-I levels affected somatotropic parameters, but not the onset of sexual functio

Constitution d'un corpus de dialogue oral pour l'évaluation automatique de la compréhension hors- et en- contexte du dialogue

Colloque avec actes et comité de lecture. internationale.International audienceThis paper presents and reports on the progress of the EVALDA/MEDIA project, focusing on the recording protocol of the reference dialogue corpus. The aim of this project is to define and test an evaluation methodology that assess and diagnose the contextsensitive understanding capability of spoken language dialogue systems. Systems from both academic organizations (CLIPS, IRIT, LIA, LIMSI, LORIA, VALORIA) and industrial sites (FRANCE TELECOM R et D, TELIP) will be evaluated. ELDA is the coordinator of the Technolangue/EVALDA multicampaign evaluation project, a national initiative sponsored by the French government, of which MEDIA is a sub-campaign. MEDIA began in January 2003. VECSYS provides the recording platform for the project

Metabolic compartmentalization in the human cortex and hippocampus: evidence for a cell- and region-specific localization of lactate dehydrogenase 5 and pyruvate dehydrogenase

BACKGROUND: For a long time now, glucose has been thought to be the main, if not the sole substrate for brain energy metabolism. Recent data nevertheless suggest that other molecules, such as monocarboxylates (lactate and pyruvate mainly) could be suitable substrates. Although monocarboxylates poorly cross the blood brain barrier (BBB), such substrates could replace glucose if produced locally.The two key enzymatiques systems required for the production of these monocarboxylates are lactate dehydrogenase (LDH; EC1.1.1.27) that catalyses the interconversion of lactate and pyruvate and the pyruvate dehydrogenase complex that irreversibly funnels pyruvate towards the mitochondrial TCA and oxydative phosphorylation. RESULTS: In this article, we show, with monoclonal antibodies applied to post-mortem human brain tissues, that the typically glycolytic isoenzyme of lactate dehydrogenase (LDH-5; also called LDHA or LDHM) is selectively present in astrocytes, and not in neurons, whereas pyruvate dehydrogenase (PDH) is mainly detected in neurons and barely in astrocytes. At the regional level, the distribution of the LDH-5 immunoreactive astrocytes is laminar and corresponds to regions of maximal 2-deoxyglucose uptake in the occipital cortex and hippocampus. In hippocampus, we observed that the distribution of the oxidative enzyme PDH was enriched in the neurons of the stratum pyramidale and stratum granulosum of CA1 through CA4, whereas the glycolytic enzyme LDH-5 was enriched in astrocytes of the stratum moleculare, the alveus and the white matter, revealing not only cellular, but also regional, selective distributions. The fact that LDH-5 immunoreactivity was high in astrocytes and occurred in regions where the highest uptake of 2-deoxyglucose was observed suggests that glucose uptake followed by lactate production may principally occur in these regions. CONCLUSION: These observations reveal a metabolic segregation, not only at the cellular but also at the regional level, that support the notion of metabolic compartmentalization between astrocytes and neurons, whereby lactate produced by astrocytes could be oxidized by neurons

A chemical survey of exoplanets with ARIEL

Thousands of exoplanets have now been discovered with a huge range of masses, sizes and orbits: from rocky Earth-like planets to large gas giants grazing the surface of their host star. However, the essential nature of these exoplanets remains largely mysterious: there is no known, discernible pattern linking the presence, size, or orbital parameters of a planet to the nature of its parent star. We have little idea whether the chemistry of a planet is linked to its formation environment, or whether the type of host star drives the physics and chemistry of the planet’s birth, and evolution. ARIEL was conceived to observe a large number (~1000) of transiting planets for statistical understanding, including gas giants, Neptunes, super-Earths and Earth-size planets around a range of host star types using transit spectroscopy in the 1.25–7.8 μm spectral range and multiple narrow-band photometry in the optical. ARIEL will focus on warm and hot planets to take advantage of their well-mixed atmospheres which should show minimal condensation and sequestration of high-Z materials compared to their colder Solar System siblings. Said warm and hot atmospheres are expected to be more representative of the planetary bulk composition. Observations of these warm/hot exoplanets, and in particular of their elemental composition (especially C, O, N, S, Si), will allow the understanding of the early stages of planetary and atmospheric formation during the nebular phase and the following few million years. ARIEL will thus provide a representative picture of the chemical nature of the exoplanets and relate this directly to the type and chemical environment of the host star. ARIEL is designed as a dedicated survey mission for combined-light spectroscopy, capable of observing a large and well-defined planet sample within its 4-year mission lifetime. Transit, eclipse and phase-curve spectroscopy methods, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allow us to measure atmospheric signals from the planet at levels of 10–100 part per million (ppm) relative to the star and, given the bright nature of targets, also allows more sophisticated techniques, such as eclipse mapping, to give a deeper insight into the nature of the atmosphere. These types of observations require a stable payload and satellite platform with broad, instantaneous wavelength coverage to detect many molecular species, probe the thermal structure, identify clouds and monitor the stellar activity. The wavelength range proposed covers all the expected major atmospheric gases from e.g. H2O, CO2, CH4 NH3, HCN, H2S through to the more exotic metallic compounds, such as TiO, VO, and condensed species. Simulations of ARIEL performance in conducting exoplanet surveys have been performed – using conservative estimates of mission performance and a full model of all significant noise sources in the measurement – using a list of potential ARIEL targets that incorporates the latest available exoplanet statistics. The conclusion at the end of the Phase A study, is that ARIEL – in line with the stated mission objectives – will be able to observe about 1000 exoplanets depending on the details of the adopted survey strategy, thus confirming the feasibility of the main science objectives.Peer reviewedFinal Published versio

Division and endopolyploidisation in intestinal nuclei during postnatal ontogenesis of Cae~gorhabditis elegans (Nematoda)

SUMMARY The intestinal nuclei of the free-living nematode, Caenorhabditis elegans, were examined for their DNA-content using Feulgen microdensitometry technique. An endopolyploid process was characterized and modalities were studied with regard to the postnatal ontogenesis. The process operates in apparent synchrony and each intestinal nucleus reaches a final ploidy level of 32 C (C : copy of haploid genome equivalent) in adult worm. Successive ploidy levels appear in correlation with the four stages of ecdysis occurring during nematode life. Functional significance of endopolyploidy in biological systems remains unclear. However, these results show endopolyploidization as a well defined process during ontogenesis

Distribution of neurokinin A-like and serotonin immunoreactivities within the vertical lobe complex in Sepia officinalis.

International audienceImmunohistochemistry, using antibodies raised against mammalian neurokinin A (NKA) and serotonin (5-HT), was applied in double-staining experiments to map these molecules within the vertical lobe complex (inferior frontal, superior frontal, post-frontal, vertical, subvertical and precommissural lobes). NKA-like and 5-HT immunoreactivities were detected in all the lobes of the vertical lobe complex but were never colocalized in cell bodies or fibres. Except for the cell layers of the superior frontal lobe, both types of labelled cell bodies were observed in all the lobes. Both types of immunoreactive fibres were detected in all the neuropils and interestingly revealed clear subdivisions within some lobes, e.g., 5-HT-IR fibres were more abundant in the peripheral part of the vertical lobe whereas NKA-IR ones were widely observed in both the peripheral and central parts. In cephalopods, the vertical lobe complex is involved in learning and memory; thus, our results strongly suggest that one or more NKA-like and 5-HT molecules may function as neurochemical messengers in these cognitive processes

Colocalization of delta sleep inducing peptide and luteinizing hormone releasing hormone in neurosecretory vesicles in rat median eminence

The colocalization of immunoreactivities similar to delta sleep inducing peptide (DSIP) and luteinizing hormone releasing hormone (LH-RH) was investigated by light and electron microscopic immunocytochemistry in the rat median eminence. At the light microscopic level, DSIP and LH-RH immunostained fibers, and varicosities exhibited a similar distribution pattern throughout the median eminence. Immunoreactive axons were mainly found in the lateral part of the external layer. Using an elution-restaining technique, the coexistence of LH-RH and DSIP immunoreactivities was observed in most labelled axons. To determine the intracellular localization of DSIP and LH-RH, we used double immunocytochemical labelling with species-specific antibodies and secondary antibodies conjugated to different sizes of gold particles. The two peptides were found colocalized in single axons. Immunoreactive terminals frequently showed direct membrane apposition with tanycyte processes but rare contacts with portal capillaries. No staining was observed in tanycytes and ependymal or glial elements. Moreover, we could demonstrate that LH-RH and DSIP (or a closely related molecular form) are contained not only in the same axons, but also in the same approximately 100-nm dense-core vesicles, suggesting cosecretion of these peptides

Extracellular clusterin promotes neuronal network complexity in vitro

Clusterin (apolipoprotein J), a highly conserved amphiphatic glycoprotein and chaperone, has been implicated in a wide range of physiological and pathological processes. As a secreted protein, clusterin has been shown to act extracellularly where it is involved in lipid transportation and clearance of cellular debris. Intracellularly, clusterin may regulate signal transduction and is upregulated after cell stress. After neural injury, clusterin may be involved in nerve cell survival and postinjury neuroplasticity. In this study, we investigated the role of extracellular clusterin on neuronal network complexity in vitro. Quantitative analysis of clustrin-treated neuronal cultures showed significantly higher network complexity. These findings suggest that in addition to previously demonstrated neuroprotective roles, clusterin may also be involved in neuronal process formation, elongation, and plasticity