D-SERINE CONTRIBUTES TO β-AMYLOID-DEPENDENT PATHOPHYSIOLOGYIN ALZHEIMER’S DISEASE

International audienceB fEPSP/PFV ra>o 0 0,2 0,4 0,6 0,8 1 1,2 1,4 1,6 WT 5xFAD 5xFAD/SR-/-+ D-s e ri n e + D-s e ri n e + D-s e ri n e Key regulators of the structural and funcFonal brain plasFcity, the N-methyl-D-aspartate subtype of glutamate receptors (NMDARs) requires the binding of the co-agonist D-serine to be acFvated. In Alzheimer's disease (AD), soluble oligomers of the beta-amyloid pepFde (Aßo) affect NMDARs possibly through mechanisms involving changes in D-serine levels since Aßo sFmulate in vitro the producFon of the co-agonist. In this study, we asked whether D-serine contributes in vivo to morpho-funcFonal NMDAR-related deregulaFons mediated by Aßo. Behavioral analysis combined to electrophysiological recordings at CA1/CA3 hippocampal synapses have been thus conducted in the 5xFAD transgenic mice model of amyloïdogenesis displaying marked increase in Aßo rates and compared to 5xFAD animals in which the homozygous gene of the serine racemase (SR) that synthesizes D-serine, has been jointly invalidated. Our results therefore show that deleFon of serine racemase prevents memory-related behavioral deficits observed in mice with prominent features of amyloidogenesis as well as impairment of NMDAR-dependent funcFonal plasFcity, suggesFng a significant contribuFon of D-serine in NMDAR-dependent β-amyloid-related pathophysiology of Alzheimer's disease. EXPERIMENTAL PROCEDURES 1) Behavioral analysis: 8-min spontaneous alternaFon test was performed in a Y maze apparatus to assess working memory performances in 10-12 months of aged mice. Successive entry of the three arms of the maze was considered as an alternaFon. The percentage of alternaFon was calculated as follows: number of alternaFons / (total number of arms visited-2) x 100. 2) Electrophysiology: Hippocampal slices (400 µm thickness) were cut from two groups of WT, 5xFAD/SR +/+ and 5xFAD/SR-/-mice aged 3-4 or 10-12 months. Field excitatory postsynapFc potenFals (fEPSPs) and presynapFc fiber volley (PFV) were extracellularly recorded in CA1 stratum radiatum aner electrical sFmulaFon of Schaffer collaterals. Input/output curves of the fEPSP/PFV raFo of isolated NMDAr-mediated fEPSPs were constructed in a low magnesium medium supplemented with the non-NMDAr antagonist NBQX (10µM) before and 15 min aner addiFon of D-serine (100 µM). High frequency (HFS)-induced long-term potenFaFon (LTP) was studied in control medium aner tetanic sFmulaFon consisFng in one train at 100 Hz delivered for 1 sec. TesFng sFmulaFon was then resumed for 60 min aner HFS. 3) Semi-quanFtaFve immunoblopng analysis: Hippocampal Fssue was homogenized in protein lysis buffer. The membranes were probed with anFbodiesaginst GluN1 (1:750

New 3-hit model of schizophrenia: behavioral and electrophysiological investigations

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PADRÃO DE ATIVIDADE DIURNA DO CAVALO-MARINHO Hippocampus reidi NO ESTADO DO RIO DE JANEIRO

The objective of this study was to characterize the diurnal patterns ofactivity of Hippocampus reidi and determine its behavioral repertoire during this period of activity. Behavioral observations were made between 07:00h and 19:30h at five different sites in Rio de Janeiro state, during whichall recorded behaviors of each observed individual were quantified over one hour. A total of 90h of observation were made, 30h for females, 30h for pregnant males and 30h for non-pregnant males. The results suggest thatseahorses are very active during the day. Swimming and foraging were the most frequent behaviors observed. Non-pregnant males presented a similar behavioral repertoire to females, while pregnant males were lessactive during the day.El presente estudio tuvo como objetivo caracterizar el patrón de actividaddiurno de la especie de caballito de mar Hippocampus reidi, si la esta presenta picos de actividad y cuáles son los comportamientos relacionados a la actividad diurna. Fueron realizadas observaciones del comportamiento entre las 07:00h y las 19:30h en cinco playas del estado de Rio de Janeiro, observando los comportamientos presentes y la duración de cada comportamiento a lo largo de una hora para cada individuo observado. Fueron realizadas un total de 90h, siendo 30 para hembras, 30 para machos incubando y 30 para machos no incubando. Los caballitos de mar presentaron un comportamiento bastante activo a lo largo de todo o período de observación, siendo los comportamientos de natación y alimentación los más frecuentes. Los machos que no estaban en estado de incubación mostraron un comportamiento activo similar al de las hembras. Por otro lado los machos en estado de incubación se mostraron poco activos a lo largo de todo el día.O presente estudo teve como objetivo caracterizar o padrão de atividade durante o período diurno da espécie de cavalo-marinho Hippocampus reidi, se a mesma apresenta picos de atividade e quais são os comportamentos relacionados a esta atividade diurna. Foram realizadas observações comportamentais de 07:00h às 19:30h em cinco praias do estado do Rio de Janeiro, observando os comportamentos presentes e a duração de cada comportamento ao longo de uma hora para cada indivíduo observado. Foi realizado um total de 90h, sendo 30 para fêmeas, 30 para machos incubando e 30 para machos não incubando. Os cavalos-marinhos apresentaram comportamento bastante ativo ao longo de todo o período de observação, sendo os comportamentos de natação e alimentação os mais freqüentes. Os machos que não estavam em estado de incubação mostraram comportamento ativo similar ao das fêmeas. Por outro lado os machos em estado de incubação mostraram-se pouco ativos ao longo de todo o dia

Altering glutamate transmission in combination with an early post-natal stress to mimic schizophrenia in male and female mice

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IMPACT OF D-SERINE DEPLETION IN THE β-AMYLOID CASCADERELATED TO ALZHEIMER’S DISEASE

International audienceD-serine, as a co-agonist of N-methyl-D-aspartate subtype of glutamate receptors (NMDAR), is a key regulator of their activation and hence involves in functional brain plasticity and memory process. The homeostasis of these receptors is affected by soluble oligomers of the beta-amyloid peptide (Aß) in Alzheimer´s disease (AD). In the course of AD, early functional dysregulations of NMDAR are well known, even though contribution of D-serine remains so far to be determined. In 3-4 month-old transgenic mice model of amyloïdogenesis (5xFAD) showing marked increase in Aß rates and apparent unaffected D-serine levels, extracellular electrophysiological recordings reveal impaired NMDAR-dependent long-term potentiation at CA1/CA3 hippocampal synapses, without significant changes in basal synaptic transmission. This deficit persists at 12 month of age when amyloid deposits are present with concomitant disabilities in cognitive functions. Generating 5xFAD mice with depletion of D-serine (through invalidation of the synthesis enzyme: Serine Racemase), we observed that these functional alterations and the long-term behavioral impairment were prevented whereas Aßo rates remain significantly elevated and comparable to 5xAFD mice. Therefore, these results provide convincing evidence for a critical and transient involvement of D-serine in hippocampal network dysfunctions and related cognitive disabilities driven by increased amyloidogenesis

D-­‐SERINE IS INVOLVED IN THE β-­‐AMYLOID-­‐RELATED PATHOPHYSIOLOGYIN ALZHEIMER’S DISEASE

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Turbulent Combustion of Polydisperse Evaporating Sprays with Droplet Crossing: Eulerian Modeling and Validation in the Infinite Knudsen Limit

The accurate simulation of the dynamics of polydisperse evaporating sprays in unsteady gaseous flows with large-scale vortical structures is both a crucial issue for industrial applications and a challenge for modeling and scientific computing. The difficulties encountered by the usual Lagrangian approaches make the use of Eulerian models attractive, aiming at a lower cost and an easier coupling with the carrier gaseous phase. Among these models, the multi-fluid model allows for a detailed description of the polydispersity and size-velocity correlations for droplets of various sizes. The purpose of the present study is twofold. First, we extend the multi-fluid model in order to cope with crossing droplet trajectories by using the quadrature method of moments in velocity phase space conditioned by size. We identify the numerical difficulties and provide dedicated numerical schemes in order to preserve the velocity moment space. Second, we conduct a comparison study and demonstrate the capability of such an approach to capture the dynamics of an evaporating polydisperse spray in a 2-D free jet configuration. We evaluate the accuracy and computational cost of Eulerian models and related discretization schemes vs. Lagrangian solvers and show that, even for finite Stokes number, the standard Eulerian multi-fluid model can be accurate at reasonable cost

The ash mass load of volcanic plumes: retrievals from a new millimeter-wave radar at Stromboli and Sabancaya volcanoes

In the framework of the French Government Laboratory of Excellence ClerVolc initiative, two experiments using a new millimeter-wave radar were carried out to retrieve various physical properties of the ash plumes, especially the mass loading parameters which are critical for the modelling of ash dispersal, as well as to study the internal dynamics of the plumes and their fallout. First measurements at Stromboli in 2015 using a 95 GHz cloud radar prototype with a fixed beam pointing above the crater characterized the distribution of plume internal reflectivities, plume widths and durations at unprecedented space-time resolutions. Combining radar in situ measurements with data modelling from a disdrometer and ash sampling on the ground further allowed the retrieval of ash concentration and gradients inside the plumes, and sometimes proximal fallout. Plume maximum ash concentration range from 1 mg/m3 to about 1 g/m3. Structuration of ash concentration with variations by a factor of 3 was also found to occur inside the falling ash in correlation with variations in the sedimentation rate measured on the ground by the disdrometer. New results from radar measurements inside stronger plumes and fallout at Sabancaya volcano (Peru, May 2018) using volume scans will also be presented