Astrocytic gap junctional communication is reduced in amyloid-β-treated cultured astrocytes, but not in Alzheimer's disease transgenic mice

Alzheimer's disease is characterized by accumulation of amyloid deposits in brain, progressive cognitive deficits and reduced glucose utilization. Many consequences of the disease are attributed to neuronal dysfunction, but roles of astrocytes in its pathogenesis are not well understood. Astrocytes are extensively coupled via gap junctions, and abnormal trafficking of metabolites and signalling molecules within astrocytic syncytia could alter functional interactions among cells comprising the neurovascular unit. To evaluate the influence of amyloid-β on astrocyte gap junctional communication, cultured astrocytes were treated with monomerized amyloid-β1–40 (1 μmol/l) for intervals ranging from 2 h to 5 days, and the areas labelled by test compounds were determined by impaling a single astrocyte with a micropipette and diffusion of material into coupled cells. Amyloid-β-treated astrocytes had rapid, sustained 50–70% reductions in the area labelled by Lucifer Yellow, anionic Alexa Fluor® dyes and energy-related compounds, 6-NBDG (a fluorescent glucose analogue), NADH and NADPH. Amyloid-β treatment also caused a transient increase in oxidative stress. In striking contrast with these results, spreading of Lucifer Yellow within astrocytic networks in brain slices from three regions of 8.5–14-month-old control and transgenic Alzheimer's model mice was variable, labelling 10–2000 cells; there were no statistically significant differences in the number of dye-labelled cells among the groups or with age. Thus amyloid-induced dysfunction of gap junctional communication in cultured astrocytes does not reflect the maintenance of dye transfer through astrocytic syncytial networks in transgenic mice; the pathophysiology of Alzheimer's disease is not appropriately represented by the cell culture system

Improving the efficiency of feed utilization in poultry by selection. 2. Genetic parameters of excretion traits and correlations with anatomy of the gastro-intestinal tract and digestive efficiency

<p>Abstract</p> <p>Background</p> <p>Poultry production has been widely criticized for its negative environmental impact related to the quantity of manure produced and to its nitrogen and phosphorus content. In this study, we investigated which traits related to excretion could be used to select chickens for lower environmental pollution.</p> <p>The genetic parameters of several excretion traits were estimated on 630 chickens originating from 2 chicken lines divergently selected on apparent metabolisable energy corrected for zero nitrogen (AMEn) at constant body weight. The quantity of excreta relative to feed consumption (CDUDM), the nitrogen and phosphorus excreted, the nitrogen to phosphorus ratio and the water content of excreta were measured, and the consequences of such selection on performance and gastro-intestinal tract (GIT) characteristics estimated. The genetic correlations between excretion, GIT and performance traits were established.</p> <p>Results</p> <p>Heritability estimates were high for CDUDM and the nitrogen excretion rate (0.30 and 0.29, respectively). The other excretion measurements showed low to moderate heritability estimates, ranging from 0.10 for excreta water content to 0.22 for the phosphorus excretion rate. Except for the excreta water content, the CDUDM was highly correlated with the excretion traits, ranging from -0.64 to -1.00. The genetic correlations between AMEn or CDUDM and the GIT characteristics were very similar and showed that a decrease in chicken excretion involves an increase in weight of the upper part of the GIT, and a decrease in the weight of the small intestine.</p> <p>Conclusion</p> <p>In order to limit the environmental impact of chicken production, AMEn and CDUDM seem to be more suitable criteria to include in selection schemes than feed efficiency traits.</p

Improving the efficiency of feed utilization in poultry by selection. 1. Genetic parameters of anatomy of the gastro-intestinal tract and digestive efficiency

<p>Abstract</p> <p>Background</p> <p>Feed costs represent about 70% of the costs of raising broilers. The main way to decrease these costs is to improve feed efficiency by modification of diet formulation, but one other possibility would be to use genetic selection. Understanding the genetic architecture of the gastro-intestinal tract (GIT) and the impact of the selection criterion on the GIT would be of particular interest. We therefore studied the genetic parameters of AMEn (Apparent metabolisable energy corrected for zero nitrogen balance), feed efficiency, and GIT traits in chickens.</p> <p>Genetic parameters were estimated for 630 broiler chickens of the eighth generation of a divergent selection experiment on AMEn. Birds were reared until 23 d of age and fed a wheat-based diet. The traits measured were body weight (BW), feed conversion ratio (FCR), AMEn, weights of crop, liver, gizzard and proventriculus, and weight, length and density of the duodenum, jejunum and ileum.</p> <p>Results</p> <p>The heritability estimates of BW, FCR and AMEn were moderate. The heritability estimates were higher for the GIT characteristics except for the weights of the proventriculus and liver. Gizzard weight was negatively correlated with density (weight to length ratio) of duodenum, jejunum and ileum. Proventriculus and gizzard weights were more strongly correlated with AMEn than with FCR, which was not the case for intestine weight and density.</p> <p>Conclusions</p> <p>GIT traits were largely dependent on genetics and that selecting on AMEn or FCR would modify them. Phenotypic observations carried out in the divergent lines selected on AMEn were consistent with estimated genetic correlations between AMEn and GIT traits.</p

Chronic exposure to glufosinate-ammonium induces spatial memory impairments, hippocampal MRI modifications and glutamine synthetase activation in mice

International audienceGlufosinate-ammonium (GLA), the active compound of a worldwide-used herbicide, acts by inhibiting the plant glutamine synthetase (GS) leading to a lethal accumulation of ammonia. GS plays a pivotal role in the mammalian brain where it allows neurotransmitter glutamate recycling within astroglia. Clinical studies report that an acute GLA ingestion induces convulsions and memory impairment in humans. Toxicological studies performed at doses used for herbicidal activity showed that GLA is probably harmless at short or medium range periods. However, effects of low doses of GLA on chronically exposed subjects are not known. In our study, C57BL/6J mice were treated during 10 weeks three times a week with 2.5, 5 and 10 mg/kg of GLA. Effects of this chronic treatment were assessed at behavioral, structural and metabolic levels by using tests of spatial memory, locomotor activity and anxiety, hippocampal magnetic resonance imaging (MRI) texture analysis, and hippocampal GS activity assay, respectively. Chronic GLA treatments have effects neither on anxiety nor on locomotor activity of mice but at 5 and 10 mg/kg induce (1) mild memory impairments, (2) a modification of hippocampal texture and (3) a significant increase in hippocampal GS activity. It is suggested that these modifications may be causally linked one to another. Since glutamate is the main neurotransmitter in hippocampus where it plays a crucial role in spatial memory, hippocampal MRI texture and spatial memory alterations might be the consequences of hippocampal glutamate homeostasis modification revealed by increased GS activity in hippocampus. The present study provides the first data that show cerebral alterations after chronic exposure to GLA

Chan-Vese based method to segment mouse brain MRI images: application to cerebral malformation analysis in trisomy 21

International audienceIn this paper, a semi automatic active contour method based on Chan-Vese model is proposed for the segmentation of mouse brain MR images. First, a 2 ½ D strategy is applied on the axial images to segment the 3D volume of interest. The method takes into account the special shape of the object to segment. Moreover, the user defines the limits where to search these contours and also provides an initial contour. This semi automatic method makes that human intervention is limited and the tedious manual handling is greatly reduced. Results have shown that the brain volumes estimated by the method are identical to expert manually estimated volumes. Last but not least, the new method was used in the analysis of the cerebral malformations linked to Trisomy 21: no significant difference of the brain volumes between Tri-somy 21 mice and the control ones were found

Rescue of fragile X syndrome phenotypes in Fmr1 KO mice by a BKCa channel opener molecule.

International audienc

Electrochemical oxidation of amoxicillin in its pharmaceutical formulation at boron doped diamond (BDD) electrode

In this work, voltammetric andelectrolysis experiments have been carried out on a conductive boron dopeddiamond (BDD) electrode in solution containing amoxicillin in itspharmaceutical formulation. The physical characterization of the BDD surface byscanning electron microscopy (SEM) reveals a polycrystalline structure withgrain sizes ranging between 0.3 and 0.6 µm. With Raman spectroscopy, BDDsurface is composed of diamons (Csp3) type carbon (Csp3)and graphitic type carbon (Csp2). The electrochemical characterization of the BDD electrode in sulfuric acid electrolyte showed a wide potential window worthing 2.74 V. The oxidation of Amoxicillin showed an irreversible anodic wave on the voltammogram in the domain of water stability indicating a direct oxidation of amoxicillin at BDD surface. The treatment of Amoxicillin in the synthetic wastewaters under various constant current densities 20, 50, 100, 135 mA cm-2 on BDD showed that Amoxicillin is highly reducedunder 100 mA cm-2 reaching 92% of the Chemical Oxygen Demand (COD)removal after 5 h of electrolysis. Investigation performed in perchloric acidas supporting electrolyte led to 87% of COD removal after 5 h of electrolysis.Mineralization of amoxicillin occurs on BDD and the chemical oxygen demandremoval was higher in sulfuric acid than in perchloric acid owing to theinvolvement of the in-situ formed persulfate and perchlorate to the degradation process mainly in the bulkof the solution. The instantaneous current efficiency (ICE) presents anexponential decay indicating that the process was limited by diffusion. Thespecific energy consumed after 5h of the amoxicillin electrolysis was 0.096 kWh COD-1and 0.035 kWh COD-1 in sulfuric acid and in perchloric acidrespectively

Dual imaging gold nanoplatforms for targeted radiotheranostics

Gold nanoparticles (AuNPs) are interesting for the design of new cancer theranostic tools, mainly due to their biocompatibility, easy molecular vectorization, and good biological half-life. Herein, we report a gold nanoparticle platform as a bimodal imaging probe, capable of coordinating Gd3+ for Magnetic Resonance Imaging (MRI) and 67Ga3+ for Single Photon Emission Computed Tomography (SPECT) imaging. Our AuNPs carry a bombesin analogue with anity towards the gastrin releasing peptide receptor (GRPr), overexpressed in a variety of human cancer cells, namely PC3 prostate cancer cells. The potential of these multimodal imaging nanoconstructs was thoroughly investigated by the assessment of their magnetic properties, in vitro cellular uptake, biodistribution, and radiosensitisation assays. The relaxometric properties predict a potential T1-and T2-MRI application. The promising in vitro cellular uptake of 67Ga/Gd-based bombesin containing particles was confirmed through biodistribution studies in tumor bearing mice, indicating their integrity and ability to target the GRPr. Radiosensitization studies revealed the therapeutic potential of the nanoparticles. Moreover, the DOTA chelating unit moiety versatility gives a high theranostic potential through the coordination of other therapeutically interesting radiometals. Altogether, our nanoparticles are interesting nanomaterial for theranostic application and as bimodal T1-and T2-MRI / SPECT imaging probes.This research was funded by FCT (Portuguese Foundation for Science and Technology), grant numbers EXCL/QEQ-MED/0233/2012, UID/Multi/04349/2013 and PTDC/MED-QUI/29649/2017. CFGCG and MMCAC thank FCT and FEDER through the COMPETE Program for funding the CQC (UID/QUI/00313/2013 and PEst-OE/QUI/UI0313/2014). P.L-L. thanks Ministry of Economy, Industry and Competitiviy for SAF2017-83043-R, and Comunity of Madrid, FEDER and FSE for S2017/BMD-368

The impact of image dynamic range on texture classification of brain white matter

<p>Abstract</p> <p>Background</p> <p>The Greylevel Cooccurrence Matrix method (COM) is one of the most promising methods used in Texture Analysis of Magnetic Resonance Images. This method provides statistical information about the spatial distribution of greylevels in the image which can be used for classification of different tissue regions. Optimizing the size and complexity of the COM has the potential to enhance the reliability of Texture Analysis results. In this paper we investigate the effect of matrix size and calculation approach on the ability of COM to discriminate between peritumoral white matter and other white matter regions.</p> <p>Method</p> <p>MR images were obtained from patients with histologically confirmed brain glioblastoma using MRI at 3-T giving isotropic resolution of 1 mm³. Three Regions of Interest (ROI) were outlined in visually normal white matter on three image slices based on relative distance from the tumor: one peritumoral white matter region and two distant white matter regions on both hemispheres. Volumes of Interest (VOI) were composed from the three slices. Two different calculation approaches for COM were used: i) Classical approach (CCOM) on each individual ROI, and ii) Three Dimensional approach (3DCOM) calculated on VOIs. For, each calculation approach five dynamic ranges (number of greylevels N) were investigated (N = 16, 32, 64, 128, and 256).</p> <p>Results</p> <p>Classification showed that peritumoral white matter always represents a homogenous class, separate from other white matter, regardless of the value of N or the calculation approach used. The best test measures (sensitivity and specificity) for average CCOM were obtained for N = 128. These measures were also optimal for 3DCOM with N = 128, which additionally showed a balanced tradeoff between the measures.</p> <p>Conclusion</p> <p>We conclude that the dynamic range used for COM calculation significantly influences the classification results for identical samples. In order to obtain more reliable classification results with COM, the dynamic range must be optimized to avoid too small or sparse matrices. Larger dynamic ranges for COM calculations do not necessarily give better texture results; they might increase the computation costs and limit the method performance.</p