Chronic escitalopram treatment attenuated the accelerated rapid eye movement sleep transitions after selective rapid eye movement sleep deprivation: a model-based analysis using Markov chains

BackgroundShortened rapid eye movement (REM) sleep latency and increased REM sleep amount are presumed biological markers of depression. These sleep alterations are also observable in several animal models of depression as well as during the rebound sleep after selective REM sleep deprivation (RD). Furthermore, REM sleep fragmentation is typically associated with stress procedures and anxiety. The selective serotonin reuptake inhibitor (SSRI) antidepressants reduce REM sleep time and increase REM latency after acute dosing in normal condition and even during REM rebound following RD. However, their therapeutic outcome evolves only after weeks of treatment, and the effects of chronic treatment in REM-deprived animals have not been studied yet.ResultsChronic escitalopram- (10 mg/kg/day, osmotic minipump for 24 days) or vehicle-treated rats were subjected to a 3-day-long RD on day 21 using the flower pot procedure or kept in home cage. On day 24, fronto-parietal electroencephalogram, electromyogram and motility were recorded in the first 2 h of the passive phase. The observed sleep patterns were characterized applying standard sleep metrics, by modelling the transitions between sleep phases using Markov chains and by spectral analysis.Based on Markov chain analysis, chronic escitalopram treatment attenuated the REM sleep fragmentation [accelerated transition rates between REM and non-REM (NREM) stages, decreased REM sleep residence time between two transitions] during the rebound sleep. Additionally, the antidepressant avoided the frequent awakenings during the first 30 min of recovery period. The spectral analysis showed that the SSRI prevented the RD-caused elevation in theta (5 inverted question mark9 Hz) power during slow-wave sleep. Conversely, based on the aggregate sleep metrics, escitalopram had only moderate effects and it did not significantly attenuate the REM rebound after RD.ConclusionIn conclusion, chronic SSRI treatment is capable of reducing several effects on sleep which might be the consequence of the sub-chronic stress caused by the flower pot method. These data might support the antidepressant activity of SSRIs, and may allude that investigating the rebound period following the flower pot protocol could be useful to detect antidepressant drug response. Markov analysis is a suitable method to study the sleep pattern

[ 18 F]fluoroethoxy-benzovesamicol, a PET radiotracer for the vesicular acetylcholine transporter and cholinergic synapses

Loss of cholinergic transmission in the cortex and hippocampus is a characteristic feature of Alzheimer's disease, and visualization of functional cholinergic synapses in the brain with PET could be a useful method for studying this degenerative condition in living humans. We investigated [ 18 F]fluoroethoxybenzovesamicol, (−)-[ 18 F]FEOBV, (−)-(2R,3R)-trans-2-hydroxy-3-(4-phenylpiperidino)-5-(2-[ 18 F]fluoroethoxy)-1,2,3,4-tetralin, a high affinity positron emitting ligand for the vesicular acetylcholine transporter, as a potential in vivo cholinergic synapse mapping agent. Rodent biodistribution, dosimetry, stereospecificity of biological effects, pharmacologic blocking studies, in vivo rodent brain autoradiography and metabolites were examined. (−)-[ 18 F]FEOBV brain uptake following intravenous injection was robust, with 2.65% dose/brain in mice at 5 min, and the regional localization matched the known distributions of presynaptic cholinergic markers at later times. Both the cholinergic localization and curare-like effects of FEOBV were associated with the “(−)”-enantiomer exclusively. (−)-[ 18 F]FEOBV regional brain distribution in rodents was changed little by pretreatment with haloperidol, (+)-3-PPP, or E-2020, indicating FEOBV, unlike other vesamicol analogs, did not interact in vivo with dopamine or σ receptor systems. Autoradiography of rat brain 3 h following i.v. injection of (−)-[ 18 F]FEOBV showed high localization in brain areas rich in presynaptic cholinergic elements. Metabolic defluorination in rodents was modest, and analysis of brain tissue following tracer administration found FEOBV as the only extractable radioactive species. (−)-[ 18 F]FEOBV dosimetry calculated from rat data estimate 10 mCi doses can be given to humans. These studies show FEOBV maps cholinergic areas with high specificity in vivo, and may provide a noninvasive means to safely and accurately gauge the functional integrity of cholinergic synapses in man using PET. Synapse 30:263–274, 1998. © 1998 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34984/1/4_ftp.pd

Heterodimerization of serotonin receptors 5-HT1A and 5-HT7 differentially regulates receptor signalling and trafficking

Serotonin receptors 5-HT1A and 5-HT7 are highly coexpressed in brain regions implicated in depression. However, their functional interaction has not been established. In the present study we show that 5-HT1A and 5-HT7 receptors form heterodimers both in vitro and in vivo. Foerster resonance energy transfer-based assays revealed that, in addition to heterodimers, homodimers composed either of 5-HT1A or 5-HT7 receptors together with monomers coexist in cells. The highest affinity for complex formation was obtained for the 5-HT7–5-HT7 homodimers, followed by the 5-HT7–5-HT1A heterodimers and 5-HT1A–5-HT1A homodimers. Functionally, heterodimerization decreases 5-HT1A-receptor-mediated activation of Gi protein without affecting 5-HT7-receptor-mediated signalling. Moreover, heterodimerization markedly decreases the ability of the 5-HT1A receptor to activate G-protein-gated inwardly rectifying potassium channels in a heterologous system. The inhibitory effect on such channels was also preserved in hippocampal neurons, demonstrating a physiological relevance of heteromerization in vivo. In addition, heterodimerization is crucially involved in initiation of the serotonin-mediated 5-HT1A receptor internalization and also enhances the ability of the 5-HT1A receptor to activate the mitogen-activated protein kinases. Finally, we found that production of 5-HT7 receptors in the hippocampus continuously decreases during postnatal development, indicating that the relative concentration of 5-HT1A–5-HT7 heterodimers and, consequently, their functional importance undergoes pronounced developmental changes

Luminescent Tris(8-hydroxyquinolates) of Bismuth(III)

Luminescent homoleptic bismuth(III) complexes have been synthesized by adding several functionalized 8-hydroxyquinolate ligands to bismuth(III) chloride in a 3:1 mole ratio in either ethanol or tetrahydrofuran (THF) solvent. These complexes have been characterized by single-crystal X-ray diffraction (XRD) analysis, UV-vis spectroscopy, fluorescence spectroscopy, and density functional theory (DFT) calculations to determine their structures and photophysical properties. Reversible dimerization of the mononuclear tris(hydroxyquinolate) complexes was observed in solution and quantified using UV-vis spectroscopy. The fluorescence spectra show a blue shift for the monomer compared with homoleptic aluminum(III) hydroxyquinolate compounds. Four dimeric compounds and one monomeric isomer were characterized structurally. The bismuth(III) centers in the dimers are bridged by two oxygen atoms from the substituted hydroxyquinolate ligands. The more sterically hindered quinolate complex, tris(2-(diethoxymethyl)-8-quinolinato)bismuth, crystallizes as a monomer. The complexes all exhibit low-lying absorption and emission spectral features attributable to transitions between the HOMO (π orbital localized on the quinolate phenoxide ring) and LUMO (π* orbital localized on the quinolate pyridyl ring). Excitation and emission spectra show a concentration dependence in solution that suggests that a monomer-dimer equilibrium occurs. Electronic structure DFT calculations support trends seen in the experimental results with a HOMO-LUMO gap of 2.156 eV calculated for the monomer that is significantly larger than those for the dimers (1.772 and 1.915 eV). The close face to face approach of two quinolate rings in the dimer destabilizes the uppermost occupied quinolate π orbitals, which reduces the HOMO-LUMO gap and results in longer wavelength absorption and emission spectral features than in the monomer form

Water hammer with column separation: A historical review

Column separation refers to the breaking of liquid columns in fully filled pipelines. This may occur in a water-hammer event when the pressure in a pipeline drops to the vapor pressure at specific locations such as closed ends, high points or knees (changes in pipe slope). The liquid columns are separated by a vapor cavity that grows and diminishes according to the dynamics of the system. The collision of two liquid columns, or of one liquid column with a closed end, may cause a large and nearly instantaneous rise in pressure. This pressure rise travels through the entire pipeline and forms a severe load for hydraulic machinery, individual pipes and supporting structures. The situation is even worse: in one water-hammer event many repetitions of cavity formation and collapse may occur. This paper reviews water hammer with column separation from the discovery of the phenomenon in the late 19th century, the recognition of its danger in the 1930s, the development of numerical methods in the 1960s and 1970s, to the standard models used in commercial software packages in the late 20th century. A comprehensive survey of laboratory tests and field measurements is given. The review focuses on transient vaporous cavitation. Gaseous cavitation and steam condensation are beyond the scope of the paper. © 2005 Elsevier Ltd. All rights reserved.A. Bergant, A.R. Simpson, and A.S. Tijsselinghttp://www.elsevier.com/wps/find/journaldescription.cws_home/622877/description#descriptio

La part des hommes. Une société de chasse au bois

The Men's Share : A Woodland Hunting Society The author shows how hunting, in a forest village in the Bourgogne, has marked, during a clearly delimited historical period, the accession of the men to a truly collective life : pooling and redistribution of duties and the products of hunting, communal meals, etc.L'auteur montre comment la chasse, dans un village forestier de la Bourgogne, a marqué, pendant une période historique bien délimitée, l'accession des hommes à une véritable vie collective : mise en commun et redistribution des postes et des produits de la chasse, repas en commun...Jolas Tina. La part des hommes. Une société de chasse au bois. In: Études rurales, n°87-88, 1982. La chasse et la cueillette aujourd'hui. pp. 345-356