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1.
Solenn Percelay Jean-Marie Billard Thomas Freret Annie Andrieux Michel Boulouard Valentine Bouet 《International journal of molecular sciences》2021,22(5)
For a better translation from treatment designs of schizophrenia to clinical efficiency, there is a crucial need to refine preclinical animal models. In order to consider the multifactorial nature of the disorder, a new mouse model associating three factors (genetic susceptibility—partial deletion of the MAP6 gene, early-life stress—maternal separation, and pharmacological treatment—chronic Δ-9-tetrahydrocannabinol during adolescence) has recently been described. While this model depicts a schizophrenia-like phenotype, the neurobiological correlates remain unknown. Synaptic transmission and functional plasticity of the CA1 hippocampal region of male and female 3-hit mice were therefore investigated using electrophysiological recordings on the hippocampus slice. While basal excitatory transmission remained unaffected, NMDA receptor (NMDAr)-mediated long-term potentiation (LTP) triggered by theta-burst (TBS) but not by high-frequency (HFS) stimulation was impaired in 3-hit mice. Isolated NMDAr activation was not affected or even increased in female 3-hit mice, revealing a sexual dimorphism. Considering that the regulation of LTP is more prone to inhibitory tone if triggered by TBS than by HFS, the weaker potentiation in 3-hit mice suggests a deficiency of intrinsic GABA regulatory mechanisms. Indeed, NMDAr activation was increased by GABAA receptor blockade in wild-type but not in 3-hit mice. This electrophysiological study highlights dysregulations of functional properties and plasticity in hippocampal networks of 3-hit mice, one of the mechanisms suspected to contribute to the pathophysiology of schizophrenia. It also shows differences between males and females, supporting the sexual dimorphism observed in the disorder. Combined with the previously reported study, the present data reinforce the face validity of the 3-hit model that will help to consider new therapeutic strategies for psychosis. 相似文献
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MB Heyman JM LaBerge KA Somberg P Rosenthal C Mudge EJ Ring JD Snyder 《Canadian Metallurgical Quarterly》1997,131(6):914-919
The transjugular intrahepatic portosystemic shunt procedure is an accepted treatment for adults with complications of portal hypertension. We performed a retrospective review of all pediatric TIPS placements performed at the University of California, San Francisco between 1990 and 1996. Twelve procedures were attempted in nine children, with a mean age (+/- SD) of 9.4 +/- 3.9 years (range, 5 to 15 years) and a mean weight of 31 +/- 18 kg (range, 16 to 70 kg). The indications for TIPS placement were portal hypertension complicated by chronic variceal hemorrhage not controlled with sclerotherapy (n = 7) and hypersplenism with thrombocytopenia (n = 2). TIPS placement was successfully completed initially in seven of nine (78%) patients. Unfavorable vascular anatomy was the cause of failure in two cases. The seven patients who underwent successful TIPS placement were followed up for an average of 136 days (range, 1 to 800 days); two still have patent shunts, three underwent liver transplantation, one had a splenorenal shunt after stenosis, and one died of underlying liver disease. Variceal bleeding was controlled in four of five patients who successfully underwent TIPS placement. Shunt occlusion occurred in four patients; patency was restored by transjugular shunt revision in three, and a splenorenal shunt was performed in one. 相似文献
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Gastric bacteria from cheetahs with gastritis were used to inoculate specific-pathogen free kittens and conventional mice. Helicobacter sp. and Gastrospirillum sp. colonized kittens, while only Gastrospirillum sp. colonized mice. In kittens, both bacterial species induced mild lymphofolliclar gastritis which did not change over the course of the 11 months observation period. In mice, Gastrospirillum sp. induced lymphoplasmacytic and follicular gastritis which increased in severity over 6 months and persisted for the 12 month observation period. Gastric ulcers and gastric mucosal hypertrophy were present in chronically infected mice. These results indicate that host but not bacterial factors influence the severity of gastritis, and that in mice, bacterial gastritis increases in severity with time and may lead to gastric ulceration in some individuals. 相似文献
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Using meta-analysis, randomized experiments in education that either clearly did or clearly did not experience student attrition were examined for the baseline comparability of groups. Results from 35 studies suggested that after attrition, the observed measures of baseline comparability of groups did not differ more than would be expected given sampling error. The degree of either overall or differential attrition did not relate to baseline comparability, a finding that held under sensitivity analyses. Also, both overall and differential attrition rates were unrelated to posttest effect sizes. All of these analyses, however, lacked sufficient statistical power to detect small but potentially meaningful effects. Results suggest caution is warranted when applying quality scales and other blanket rules pertaining to attrition that are meant to either serve as inclusion-exclusion criteria or in scoring study quality. Much greater attention is needed to both the reporting of attrition in primary studies and to the development of conceptual and empirical models of the attrition process. These developments would aid further investigation of the relation between attrition and study outcomes. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
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KA Roberto 《Canadian Metallurgical Quarterly》1997,52(3):127-131
We investigated the effect of chlorpromazine (CPZ) in a murine model of T-cell-dependent liver injury caused by concanavalin A (ConA). CPZ (3 and 10 mg/kg) treatment 1 h before ConA injection prevented liver injury. CPZ (3, 10 mg/kg) administered 1 h after a ConA injection was also hepatoprotective, whereas cyclosporin (CsA, 100 mg/kg) was active only when given before ConA. Under either condition, CsA but not CPZ prevented concurrent increases in splenic ornithine decarboxylase (ODC) activity, a putative index of T-cell proliferation/differentiation. CPZ down-regulated tumor necrosis factor-alpha (TNF-alpha) and up-regulated IL-10 in mice that then received ConA, whereas delayed administration of CPZ had no effect. These results suggest that CPZ prevented liver injury without affecting the proliferation/differentiation of T-cells. The dissociation of hepatoprotection by CPZ from cytokine modulation indicates that this drug intervenes in the adherence of T-cells or the death of hepatocytes in the ConA-model. 相似文献
10.
FV Elmslie M Rees MP Williamson M Kerr MJ Kjeldsen KA Pang A Sundqvist ML Friis D Chadwick A Richens A Covanis M Santos A Arzimanoglou CP Panayiotopoulos D Curtis WP Whitehouse RM Gardiner 《Canadian Metallurgical Quarterly》1997,6(8):1329-1334
The epilepsies are a group of disorders characterised by recurrent seizures caused by episodes of abnormal neuronal hyperexcitability involving the brain. Up to 60 million people are affected worldwide and genetic factors may contribute to the aetiology in up to 40% of patients. The most common human genetic epilepsies display a complex pattern of inheritance. These are categorised as idiopathic in the absence of detectable structural or metabolic abnormalities. Juvenile myoclonic epilepsy (JME) is a distinctive and common variety of familial idiopathic generalised epilepsy (IGE) with a prevalence of 0.5-1.0 per 1000 and a ratio of sibling risk to population prevalence (lambda(s)) of 42. The molecular genetic basis of these familial idiopathic epilepsies is entirely unknown, but a mutation in the gene CHRNA4, encoding the alpha4 subunit of the neuronal nicotinic acetylcholine receptor (nAChR), was recently identified in a rare Mendelian variety of idiopathic epilepsy. Chromosomal regions harbouring genes for nAChR subunits were therefore tested for linkage to the JME trait in 34 pedigrees. Significant evidence for linkage with heterogeneity was found to polymorphic loci encompassing the region in which the gene encoding the alpha7 subunit of nAChR (CHRNA7) maps on chromosome 15q14 (HLOD = 4.4 at alpha = 0.65; Z(all) = 2.94, P = 0.0005). This major locus contributes to genetic susceptibility to JME in a majority of the families studied. 相似文献