Morphological changes of mitochondria-rich cells in gill of Sparidentex hasta during adaptation to different environmental salinities by scanning electron microscopy

To determine the cellular and adaptations changes in mitochondria-rich cells under different salinities, Sparidentex hasta as a urihaline has been studied.180 fish weighing 150 ± 0.5 gr and 23±1 cm length, were directly exposed to (5, 20, 40 and 60 ppt) salinities for a week. Sampling was performed on days 1, 2 and 7 and three fish from each tank (12 fish from each treatment) were sampled each time. Samples were fixed in glutaraldehyde 2/5 % solution and washed with 0.1M (pH=7.4) buffer phosphate. Samples were dehydrated in increasing ethanol series (from 50 % to pure ethanol) followed by 100 % acetone. Tissue blocks were frozen by liquid nitrogen and then immediately followed by scanning electron microscope LEO (Model 1455VP) with 15Kv voltage. Scanning electron microscope revealed three types of mitochondria-rich cells with derived apertures, shallow and deep apical openings. The number and size of mitochondria-rich cells in the apical openings in 60ppt salinity increased on the first day compared to rest of the treatments. During the experiment, the density and size of the openings in the mitochondria-rich cells in the lower salinity increased but in higher salinity of sea water size and density of openings decreased during experiment

Evaluating genetic markers and neurobiochemical analytes for fluoxetine response using a panel of mouse inbred strains

RationaleIdentification of biomarkers that establish diagnosis or treatment response is critical to the advancement of research and management of patients with depression.ObjectiveOur goal was to identify biomarkers that can potentially assess fluoxetine response and risk to poor treatment outcome.MethodsWe measured behavior, gene expression, and the levels of 36 neurobiochemical analytes across a panel of genetically diverse mouse inbred lines after chronic treatment with water or fluoxetine.ResultsGlyoxylase 1 (GLO1) and guanine nucleotide-binding protein 1 (GNB1) mostly account for baseline anxiety-like and depressive-like behavior, indicating a common biological link between depression and anxiety. Fluoxetine-induced biochemical alterations discriminated positive responders, while baseline neurobiochemical differences differentiated negative responders (p < 0.006). Results show that glial fibrillary acidic protein, S100 beta protein, GLO1, and histone deacetylase 5 contributed most to fluoxetine response. These proteins are linked within a cellular growth/proliferation pathway, suggesting the involvement of cellular genesis in fluoxetine response. Furthermore, a candidate genetic locus that associates with baseline depressive-like behavior contains a gene that encodes for cellular proliferation/adhesion molecule (Cadm1), supporting a genetic basis for the role of neuro/gliogenesis in depression.ConclusionWe provided a comprehensive analysis of behavioral, neurobiochemical, and transcriptome data across 30 mouse inbred strains that has not been accomplished before. We identified biomarkers that influence fluoxetine response, which, altogether, implicate the importance of cellular genesis in fluoxetine treatment. More broadly, this approach can be used to assess a wide range of drug response phenotypes that are challenging to address in human samples.Electronic supplementary materialThe online version of this article (doi:10.1007/s00213-011-2574-z) contains supplementary material, which is available to authorized users

Traitement des prognathies mandibulaires. Intérêt de l'étude orthodontico-chirurgicale

Les différentes étapes de traitement d'un prognathisme mandibulaire doivent être définies en commun entre le chirurgien et l'orthodontiste avant tout acte thérapeutique. Ne pas respecter ce protocole entraîne soit des récidives, soit des résultats de compromis. Les auteurs ont analysé quatre cas cliniques pour illustrer cette démarche, en présentant des moulages, des photographies et des céphalogrammes avant, pendant, et après traitement

[Creation of a line of "depressed" mice from a selection of breeders exhibiting a behavioral helplessness]

Antidepressants are used since 40 years. All presently used antidepressants have a slow onset of action and do not improve all patients; thus, there is an absolute need for new antidepressants. A variety of animal models, often based upon the monoaminergic theory of depressive disorders, has been used to screen the current antidepressants. In fact, the main focus of most of these animal models has been to predict the antidepressant potential i.e. to establish predictive validity. However, the evaluation of such animal models should also consider face validity, i.e. how closely the model resembles the human condition, and this should help to identify innovating medicines. Antidepressants, when taken by a healthy person, induce nothing more than side effects, unrelated to an action on mood, whereas they alleviate depressive symptomatology in depressed patients. We have speculated that genetically selected animal models would be closer to the human clinical situation than models based on standard laboratory strains. We have depicted here that marked differences exist between strains of mice in the amount of immobility i.e. "spontaneous helplessness" observed in the tail suspension test, a method used to screen potential antidepressants. We have studied the behavioural characteristics of mice selectively bred for spontaneous high or low immobility scores in the tail suspension test. Hopefully, these selectively bred lines will provide a novel approach to investigate behavioural, neurochemical and neuroendocrine correlates of antidepressant action

In vivo labelling of the neuronal dopamine uptake complex in the mouse striatum by [3H]GBR 12783

Various characteristics of the in vivo striatal binding of [3H]GBR 12783 (1-[2-(diphenylmethoxy)-ethyl]-4-(3-phenyl-1[3H]-2-propenyl)pipera zine), a specific ligand of the neuronal dopamine uptake complex, were determined in mice. Increasing doses of the ligand revealed the saturability of the binding at a single site with half-maximal saturation at a dose of approximately 7 mumol/kg and an apparent maximal number of binding sites (Bmax) of 12.8 pmol/mg protein in striatum. Specific binding was prevented by various dopamine uptake blockers, pyrovalerone, GBR 13069, GBR 12783, N-[1-2-benzo(b)thiophenyl)cyclohexyl] piperidine, cocaine, methylphenidate and was inhibited in a stereoselective manner by the enantiomers of nomifensine. Other drugs which are not dopamine uptake blockers either did not modify [3H]GBR 12783 binding (the diphenylbutylpiperazine derivative flupenthixol) or increased it (the diphenylpiperazine derivative flunarizine or the chemically unrelated compounds fenfluramine and SKF 525A). A close correlation was found between occupancy of the striatal [3H]GBR 12783 binding site and the stimulant locomotor effect of the drug. A similar specific striatal binding of [3H]GBR 12783 was evidenced in both NMRI and CD1 strains. It was concluded that [3H]GBR 12783 administered in vivo provides a measure of the density of dopamine uptake sites in mouse striatum

Relationship between the effects of dexamphetamine on locomotion and on striatal [3H]GBR 12783 binding in vivo

In mice, low doses (1-2-4 mg/kg s.c.) of dexamphetamine stimulated locomotor activity in a dose-dependent manner. Over the same range of doses the drug dose dependently inhibited the in vivo striatal binding of the dopamine uptake inhibitor, [3H]GBR 12783. At 3 mg/kg dexamphetamine, the stimulant effect and the inhibition of the striatal binding of [3H]GBR 12783 displayed a similar time course. Pretreatments that either increased (L-DOPA 200 mg/kg, benserazide 50 mg/kg i.p.) or decreased (reserpine 5 mg/kg s.c., alpha-methyl-p-tyrosine 200 mg/kg) striatal dopamine levels did not modify the inhibition by dexamphetamine of [3H]GBR 12783 binding in vivo. This suggests that the inhibition is due to a direct effect of dexamphetamine, not mediated by endogenous dopamine, and further that a unique site is responsible for the neuronal uptake of dexamphetamine and for the binding of pure dopamine uptake inhibitors

Comments on an animal model of depression

Depression is a multifactorial illness and genetic factors play a role in its etiology. The understanding of its pathophysiology relies on the availability of experimental models potentially mimicking the disease. Here is presented a model built up by selective breeding of mice with strikingly different responses in the tail suspension test, a stress paradigm aimed at screening potential antidepressants. Indeed, "helpless" mice are essentially immobile in the tail suspension test, as well as the Porsolt forced-swim test, and they show reduced consumption of a palatable 2% sucrose solution. In addition, helpless mice exhibit sleep-wakefulness alterations resembling those classically observed in depressed patients, notably a lighter and more fragmented sleep, with an increase pressure of rapid eye movement sleep. Compared with "nonhelpless" mice, they display higher basal serum corticosterone levels and lower serotonin metabolism index in the hippocampus. Remarkably, serotonin1A autoreceptor stimulation induced greatest hypothermia and inhibition of serotoninergic neuronal firing in the nucleus raphe dorsalis in helpless than in nonhelpless mice. Thus, helpless mice exhibit a decrease in serotoninergic tone, which evokes that associated with endogenous depression in humans. Finally, both the behavioral impairments and the serotoninergic dysfunction can be improved by chronic treatment with the antidepressant fluoxetine. The helpless line of mice may provide an opportunity to approach genes influencing susceptibility to depression and to investigate neurophysiological and neurochemical substrates underlying antidepressant effects

[The dopamine transporter characterization and physiopathologic implications]

The dopamine transporter (DAT) is the carrier protein that transports dopamine across the presynaptic membrane. The DAT terminates the action of dopamine (DA) in the synapse via reuptake and thus regulates DA neurotransmission. The transporter has been studied by direct binding techniques using a variety of ligands which are inhibitors of DA transport. DAT binding, both in vivo (positron emission tomography) and in vitro (post mortem) may serve as a presynaptic marker to measure altered DA innervation in several neuropsychiatric diseases such as idiopathic Parkinson's disease, Tourette's disease, schizophrenia or cocaine addiction. In Parkinson's disease, a reduction in the density of binding sites could be due either to a degeneration of the terminal dopaminergic projections or to a compensatory readjustment in the level of dopamine synaptic transmission. This dopaminergic cell specific marker could also aid in attempts to elucidate the rate at which dopaminergic cells are lost in this disease. MPTP (a neurotoxin which induces a parkinsonian-like syndrome after conversion in MPP+) uses DAT to enter the neuron and exert its toxic effect which may be prevented by pretreatment with DA uptake blockers. In cocaine abuse, DAT mediates the addictive properties of cocaine. Cocaine binding sites on the carrier may be distinct from DA binding sites allowing the development of medication sparing the DA function but impairing the cocaine effects. In schizophrenia, functional DA uptake was reported to be increased in the striatum in post mortem brains, whereas the kinetic parameters of the uptake sites were unchanged using different transporter labeling ligands. Thus, this marker does not provide any evidence for the dopaminergic hypothesis, but an impairment of the DAT itself could possibly be involved in the etiology of schizophrenia. However, the possible interaction of drugs such as L-Dopa or neuroleptic treatment with transporter binding may be taken into account in the results analysis. Finally, the DAT gene is also an important candidate gene for psychiatric diseases such as schizophrenia or cocaine abuse

Ionic requirements for the specific binding of [3H]GBR 12783 to a site associated with the dopamine uptake carrier

At 0 degrees C, when Na+ was the only cation present in the incubation medium, increasing the Na+ concentration from 3 to 10 mM enhanced the affinity of [3H]1-[2-(++di-phenylmethoxy)ethyl]-4-(3-phenyl-2-propenyl)piperaz ine [( 3H]GBR 12783) for the specific binding site present in rat striatal membranes without affecting the Bmax. For higher Na+ concentrations, specific binding values plateaued and then slightly decreased at 130 mM Na+. In a 10 mM Na+ medium, the KD and the Bmax were, respectively, 0.23 nM and 12.9 pmol/mg of protein. In the presence of 0.4 nM [3H]GBR 12783, the half-maximal specific binding occurred at 5 mM Na+. A similar Na+ dependence was observed at 20 degrees C. Scatchard plots indicated that K+, Ca2+, Mg2+, and Tris+ acted like competitive inhibitors of the specific binding of [3H]GBR 12783. The inhibitory potency of various cations (K+, Ca2+, Mg2+, Tris+, Li+, and choline) was enhanced when the Na+ concentration was decreased from 130 to 10 mM. In a 10 mM Na+ medium, the rank order of inhibitory potency was Ca2+ (0.13 mM) greater than Mg2+ greater than Tris+ greater than K+ (15 mM). The requirement for Na+ was rather specific, because none of the other cations acted as a substitute for Na+. No anionic requirement was found Cl-, Br-, and F- were equipotent. These results suggest that low Na+ concentrations are required for maximal binding; higher Na+ concentrations protect the specific binding site against the inhibitory effect of other cations