Éditeur(s) : Actes de colloques Ifremer, Tahiti, French Polynesia, 20 Feb - 4 Mar 1989, n°9, chap. 15, pp.143-160
Résumé : The finfish species reared in marine intensive conditions in the French Caribbean Islands are imported (European seabass, American red drum and Oreochromis hybrids) or local (Carangids and Lutjanids) species. The European seabass (Dicentrarchus labrax ) is susceptible, during its first year of life, to a contagious disease characterized by whirling and hyperexcitability, associated with severe lesions of the brain, viral particles being pointed out in the damaged nervous cells.

Droits : info:eu-repo/semantics/openAccess
http://archimer.ifremer.fr/doc/1989/acte-1478.pdf
http://archimer.ifremer.fr/doc/00000/1478/

Éditeur(s) : HAL CCSD IOS Press
Résumé : International audience
The hematocrit-to-viscosity ratio (HVR) has been widely used has an estimate of red blood cell (RBC) oxygen transport effectiveness into the microvasculature or as an oxygen delivery index. However, no study investigated the possibility of HVR to truly reflect RBC oxygen transport effectiveness or to be an oxygen delivery index. We measured blood viscosity at high shear rate (225 s −1), hematocrit, HVR, as well as the microvascular oxyhemoglobin saturation (TOI; tissue oxygen index) by spatial resolved near-infrared spectroscopy (NIRS) at cerebral and muscle levels in three population known to have various degrees of hemorheological abnormalities: healthy subjects (AA), patients with sickle cell SC disease (SC) characterized by moderate anemia and patients with sickle cell anemia (SS) marked by severe anemia. At both the cerebral and muscle level, HVR was positively correlated with TOI (r = 0.28; p = 0.03 and r = 0.38; p = 0.003, at the cerebral and muscle level, respectively). These findings suggest that HVR probably play a key role in blood flow and hemodynamic regulation in the microvasculature, hence modulating the amount of oxygen available for tissues. Nevertheless, the strengths of the associations are weak (R 2 < 0.50), suggesting that other determinants modulate microvascular blood flow and oxygenation, such as vascular geometry and vasomotor reserve.
ISSN: 1386-0291

hal-01163460
https://hal.univ-antilles.fr/hal-01163460
DOI : 10.3233/CH-131742

Éditeur(s) : European Association of Fish Pathologists (EAFP)
Résumé : High levels of mortalities (20%) associated with abnormal swimming have been observed in farmed juveniles of seabass, Dicentrarchus labrax, in Mediterranean coast, southern France. Histopathology was obvious in the brain with nervOUS tissue necrosis and the presence of ceUs containing basophilic granules corresponding to smaU coccoid organisms. Ultrastructural examination revealed these organisms were rickettsia-like organisms morphologicaUy close to Piscirickettsia salmonis
Bull. Eur. Ass. Fish Pathol. (European Association of Fish Pathologists (EAFP)), 1996 , Vol. 16 , N. 1 , P. 30-32

Droits : European Association of Fish Pathologists (EAFP)
http://archimer.ifremer.fr/doc/1996/publication-6158.PDF
http://archimer.ifremer.fr/doc/00000/6158/

Éditeur(s) : HAL CCSD
Résumé : International audience
The development of predictive tools has been commonly utilized as the most effective manner to prevent illnesses thatstrike suddenly. Within this context, investigations linking fine human motor control with brain stroke risk factors areconsidered to have a high potential but they are still in an early stage of research. The present paper analysesneuromuscular features of oscillatory movements based on the Omega-Lognormal model of the Kinematic Theory. On adatabase of oscillatory movements from 120 subjects, we demonstrate that the proposed features differ significantlybetween subjects with and without brain stroke risk factors. This promising result motivates the development ofpredictive tools based on the Omega-Lognormal model.
17th Biennial Conference of the International Graphonomics Society
Pointe-à-Pitre, Guadeloupe

hal-01165773
https://hal.univ-antilles.fr/hal-01165773
https://hal.univ-antilles.fr/hal-01165773/document
https://hal.univ-antilles.fr/hal-01165773/file/IGS_2015_submission_9.pdf

Éditeur(s) : HAL CCSD BioScientifica
Résumé : International audience
Paracetamol/acetaminophen (N-Acetyl-p-Aminophenol; APAP) is the preferred analgesic for pain relief and fever during pregnancy. It has therefore caused concern that several studies have reported that prenatal exposure to APAP results in developmental alterations in both the reproductive tract and the brain. Genitals and nervous system of male mammals are actively masculinised during foetal development and early postnatal life by the combined actions of prostaglandins and androgens, resulting in the male-typical reproductive behaviour seen in adulthood. Both androgens and prostaglandins are known to be inhibited by APAP. Through intrauterine exposure experiments in C57BL/6 mice, we found that exposure to APAP decreased neuronal number in the sexually dimorphic nucleus (SDN) of the preoptic area (POA) in the anterior hypothalamus of male adult offspring. Likewise, exposure to the environmental pollutant and precursor of APAP, aniline, resulted in a similar reduction. Decrease in neuronal number in the SDN-POA is associated with reductions in male sexual behaviour. Consistent with the changes, male mice exposed in uteri to APAP exhibited changes in urinary marking behaviour as adults and had a less aggressive territorial display towards intruders of the same gender. Additionally, exposed males had reduced intromissions and ejaculations during mating with females in oestrus. Together, these data suggest that prenatal exposure to APAP may impair male sexual behaviour in adulthood by disrupting the sexual neurobehavioral programming. These findings add to the growing body of evidence suggesting the need to limit the widespread exposure and use of APAP by pregnant women.
ISSN: 1470-1626

hal-01560285
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01560285
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01560285/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01560285/file/Prenatal%20exposures%20to%20paracetamol-accepted.pdf
DOI : 10.1530/REP-17-0165

Éditeur(s) : HAL CCSD
Résumé : International audience
The epigenetic mark 5-hydroxymethylcytosine (5hmC) is a cytosine modification that is abundant in the central nervous system of mammals and which results from 5-methylcytosine oxidation by TET enzymes. Such a mark is suggested to play key roles in the regulation of chromatin structure and gene expression. However, its precise functions still remain poorly understood and information about its distribution in non-mammalian species is still lacking. Here, the distribution of 5hmC was investigated in the brain of adult zebrafish, African claw frog, and mouse in a comparative manner. We show that zebrafish neurons are endowed with high levels of 5hmC, whereas quiescent or proliferative neural progenitors show low to undetectable levels of the modified cytosine. In the brain of larval and juvenile Xenopus, 5hmC is also detected in neurons, while ventricular proliferative cells do not display this epigenetic mark. Similarly, 5hmC is enriched in neurons compared to neural progenitors of the ventricular zone in the mouse developing cortex. Interestingly, 5hmC colocalized with the methylated DNA binding protein MeCP2 and with the active chromatin histone modification H3K4me2 in mouse neurons. Taken together, our results show an evolutionarily conserved cerebral distribution of 5hmC between fish and tetrapods and reinforce the idea that 5hmC fulfills major functions in the control of chromatin activity in vertebrate neurons. J. Comp. Neurol. 525:478-497, 2017. © 2016 Wiley Periodicals, Inc.
Journal of Comparative Neurology

hal-01439354
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01439354
DOI : 10.1002/cne.24077
PUBMED : 27414756

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
This study, conducted in the brain of a perciform fish, the European sea bass, aimed at raising antibodies against the precursor of the kisspeptins in order to map the kiss systems and to correlate the expression of kisspeptins, kiss1 and kiss2, with that of kisspeptin receptors (kiss-R1 and kiss-R2). Specific antibodies could be raised against the preprokiss2, but not the preoprokiss1. The data indicate that kiss2 neurons are mainly located in the hypothalamus and project widely to the subpallium and pallium, the preoptic region, the thalamus, the pretectal area, the optic tectum, the torus semicircularis, the mediobasal medial and caudal hypothalamus, and the neurohypophysis. These results were compared to the expression of kiss-R1 and kiss-R2 messengers, indicating a very good correlation between the wide distribution of Kiss2-positive fibers and that of kiss-R2 expressing cells. The expression of kiss-R1 messengers was more limited to the habenula, the ventral telencephalon and the proximal pars distalis of the pituitary. Attempts to characterize the phenotype of the numerous cells expressing kiss-R2 showed that neurons expressing tyrosine hydroxylase, neuropeptide Y and neuronal nitric oxide synthase are targets for kisspeptins, while GnRH1 neurons did not appear to express kiss-R1 or kiss-R2 messengers. In addition, a striking result was that all somatostatin-positive neurons expressed-kissR2. These data show that kisspeptins are likely to regulate a wide range of neuronal systems in the brain of teleosts.
ISSN: 1932-6203

hal-00877315
https://hal.archives-ouvertes.fr/hal-00877315
https://hal.archives-ouvertes.fr/hal-00877315/document
https://hal.archives-ouvertes.fr/hal-00877315/file/Expressionsur Kisspeptins-accepted.pdf
DOI : 10.1371/journal.pone.0070177

Éditeur(s) : HAL CCSD
Résumé : International audience
Estrogens and progestins are widely used in combination in human medicine and both are present in aquatic environment. Despite the joint exposure of aquatic wildlife to estrogens and progestins, very little information is available on their combined effects. In the present study we investigated the effect of ethinylestradiol (EE2) and Levonorgestrel (LNG), alone and in mixtures, on the expression of the brain specific ER-regulated cyp19a1b gene. For that purpose, recently established zebrafish-derived tools were used: (i) an in vitro transient reporter gene assay in a human glial cell line (U251-MG) co-transfected with zebrafish estrogen receptors (zfERs) and the luciferase gene under the control of the zebrafish cyp19a1b gene promoter and (ii) an in vivo bioassay using a transgenic zebrafish expressing GFP under the control of the zebrafish cyp19a1b gene promoter (cyp19a1b-GFP). Concentration-response relationships for single chemicals were modeled and used to design the mixture experiments following a ray design. The results from mixture experiments were analyzed to predict joint effects according to concentration addition and statistical approaches were used to characterize the potential interactions between the components of the mixtures (synergism/antagonism). We confirmed that some progestins could elicit estrogenic effects in fish brain. In mixtures, EE2 and LNG exerted additive estrogenic effects both in vitro and in vivo, suggesting that some environmental progestin could exert effects that will add to those of environmental (xeno-)estrogens. Moreover, our zebrafish specific assays are valuable tools that could be used in risk assessment for both single chemicals and their mixtures. © 2016 Elsevier Inc.
Toxicology and Applied Pharmacology

hal-01367151
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01367151
DOI : 10.1016/j.taap.2016.07.023
PUBMED : 27491593

Éditeur(s) : HAL CCSD Taylor & Francis
Résumé : International audience
The functional organization of the circadian system and the location of the main circadian oscillators vary through phylogeny. Present study investigates by in situ hybridization the anatomical location of the clock gene gPer1b in forebrain and midbrain, pituitary, and in two peripheral locations, the anterior intestine and liver, in a teleost fish, the goldfish (Carassius auratus). Moreover, the daily expression profiles of this gene were also studied by quantitative Real Time-PCR. Goldfish were maintained under a 12L–12D photoperiod and fed daily at 2 h after lights were switched on. A wide distribution of gPer1b mRNA in goldfish brain and pituitary was found in telencephalon, some hypothalamic nuclei (including the homologous to mammalian SCN), habenular nucleus, optic tectum, cerebellum and torus longitudinalis. Moreover, gPer1b expression was observed, for the first time in teleosts, in the pituitary, liver and anterior intestine. Day/night differences in gper1b mRNA abundance were found by in situ hybridization, with higher signal at nighttime that correlates with the results obtained by RT-PCR, where a rhythmic gPer1b expression was found in all tissues with acrophases at the end of the night. Amplitudes of gper1b rhythms vary among tissues, being higher in liver and intestine than in the brain, maybe because different cues entrain clocks in these locations. These results support the existence of functional clocks in many central and peripheral locations in goldfish coordinated, ticking at the same time
ISSN: 0742-0528

hal-01197353
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01197353
DOI : 10.3109/07420528.2015.1049615
PUBMED : 26171989

Éditeur(s) : HAL CCSD
Résumé : Benzophenone derivatives (BPs) are used as UV filters in many different products. These lipophilic compounds were recently described as ubiquitous contaminant of different compartiments of aquatic systems, including fish. In this study, we evaluated estrogenic activity of ten BPs in a model fish species, the zebrafish (Danio rerio), by combining newly developed in vitro and in vivo models. In vitro, three specific zebrafish reporter gene models expressing zebrafish estrogen receptors (ZfERs) in zebrafish hepatic cell line (ZFL) were used.Estrogenic activity of BPs was quantify in vivo by using a newly developed transgenic zebrafish line that expresses green fluorescent protein (GFP) under the control of the cyp19a1b promoter. The cyp19a1b gene codes for the brain aromatase B that is under the control of estrogens. Vitellogenin (Vtg), a marker of estrogenic compound, was used to assess the potential estrogenic effect of certain BPs in male fish. Five of 10 BPs induced an estrogenic activity on the three models: BP2, THB, BP1, 4BP, while BP and 234 BP were non active. We noted diffrence in BPs ranking depending on the zfER subtypes suggesting ?/? receptor selectivity by certain BPs. By quantifying GFP expression in live zebrafish, we confirm the estrogenic activity of some BP, i.e., BP1, THB, 4BP and 44'BP, as shown by their ability to induce GFP in a concentration-dependent manner. However, the ranking of BPs as a function of their estrogenic activity assay is different between models. For instance, 4BP was the most estrogenic compound in vivo but not in vitro. Differences were also noticed regarding the estrogenic activity of BP2. In vitro, BP2 has strong activity but had no effect on GFP in cyp19a1b-GFP embryo. However, BP2 induced strongly Vtg in male. The lack of estrogenic activity of BP2 in embryo may be related to difference of biodisponibility and/or metabolisation of this compound between embryo and adult fish. Our approach allows to characterize the estrogenic potency of emerging pollutants, using innovative in vitro and in vivo assays within a unique model fish species. The differences observed between assays deserve further studies to characterize the behavior of compounds in the different biological models in term of biodisponibility and metabolism.
1. European Conference on the Replacement, Reduction and Refinement of Animal Experiments in Ecotoxicology
Dübendorf, Switzerland

ineris-00971019
https://hal-ineris.archives-ouvertes.fr/ineris-00971019
INERIS : EN-2012-243

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
The effects of some progestins on fish reproduction have been recently reported revealing the hazard of this class of steroidal pharmaceuticals. However, their effects at the central nervous system level have been poorly studied until now. Notwithstanding, progesterone, although still widely considered primarily a sex hormone, is an important agent affecting many central nervous system functions. Herein, we investigated the effects of a large set of synthetic ligands of the nuclear progesterone receptor on the glial-specific expression of the zebrafish brain aromatase (cyp19a1b) using zebrafish mechanism-based assays. Progesterone and 24 progestins were first screened on transgenic cyp19a1b-GFP zebrafish embryos. We showed that progesterone, dydrogesterone, drospirenone and all the progesterone-derived progestins had no effect on GFP expression. Conversely, all progestins derived from 19-nortesterone induced GFP in a concentration-dependent manner with EC50 ranging from the low nM range to hundreds nM. The 19-nortestosterone derived progestins levonorgestrel (LNG) and norethindrone (NET) were further tested in a radial glial cell context using U251-MG cells co-transfected with zebrafish ER subtypes (zfER alpha, zfER beta 1 or zfER beta 2) and cyp19a1b promoter linked to luciferase. Progesterone had no effect on luciferase activity while NET and LNG induced luciferase activity that was blocked by ICI 182,780. Zebrafish-ERs competition assays showed that NET and LNG were unable to bind to ERs, suggesting that the effects of these compounds on cyp19a1b require metabolic activation prior to elicit estrogenic activity. Overall, we demonstrate that 19-nortestosterone derived progestins elicit estrogenic activity by inducing cyp19a1b expression in radial glial cells. Given the crucial role of radial glial cells and neuro-estrogens in early development of brain, the consequences of exposure of fish to these compounds require further investigation.
ISSN: 0041-008X

hal-01366373
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01366373
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01366373/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01366373/file/Several%20synthetic%20progestins%20disrupt%20the%20glial%20cell.pdf
DOI : 10.1016/j.taap.2016.05.019

Éditeur(s) : HAL CCSD Lippincott, Williams & Wilkins
Résumé : International audience
Regarding nerves as simple cables and electrical conduits is a gross error that does not allow us to understand the anomalies and disorders observed postoperatively. Instead, nerves should be seen as a living tissue of which physiological regulation is as complex as that of the blood-brain barrier. This review describes the basic structure and functions of this blood-nerve barrier and highlights the mechanisms of its breakdown and the resultant disorders. For clinical practice, it is important to note that the diffusion of molecules from the perineurium or from the blood is very limited, and so the blood-nerve barrier is a major pharmacologic barrier. Any stress upon neural physiological balance, particularly the terminal vascular blood supply, will induce the classic inflammatory cascade. Due to the complexity of the vascular system, nerve ischaemia will occur more quickly when the terminal blood supply is compromised. This blood supply can adapt in a variety of ways but when these possibilities of adaptation are exceeded, tissue ischaemia may be more extensive. Also, even after the initial injury has subsided, inflammation can cause a secondary insult. This could be particularly important in some patients with subclinical neuropathy.
ISSN: 0265-0215

hal-01477207
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01477207
DOI : 10.1097/EJA.0000000000000590
PUBMED : 28146457

Éditeur(s) : HAL CCSD Institute of Electrical and Electronics Engineers
Résumé : International audience
: A new set-up for exposure of human cells in vitro at 37°C to pulse-modulated 300 MHz and 500 MHz signals of future magnetic resonance imaging (MRI) systems is designed, built up, and characterized. Two dipole antennas, specifically designed for ultra high field MRI, are used as radiating structures. The electromagnetic (EM) field distribution inside the incubator containing the cells is computed, and it is shown to be in a good agreement with measurements. The electric field at the cell level is quantified numerically. Local, 1g average, and averaged over the culture medium volume SAR are provided along with the standard deviation values for each well. Temperature increments are measured inside the culture medium during the exposure using an optical fiber thermometer. Then we identify the pulse parameters corresponding to the thermal threshold of 1°C, usually considered as a threshold for thermally-induced biological effects. For these parameters, the induction of heat shock proteins is assessed to biologically verify a potential thermal response of cells. The data demonstrate that, under the considered experimental conditions, exposure to pulsemodulated radiations emulating typical ultra high field MRI signals, corresponding to temperature increments below 1°C, does not trigger any heat shock response in human brain cells.
ISSN: 0018-9294

hal-00874329
https://hal.archives-ouvertes.fr/hal-00874329
DOI : 10.1109/TBME.2013.2270371
PUBMED : 23799680

Éditeur(s) : HAL CCSD American Chemical Society
Résumé : International audience
Childhood absence epilepsy is a prototypic form of generalized nonconvulsive epilepsy characterized by short impairments of consciousness concomitant with synchronous and bilateral spike-and-wave discharges in the electroencephalogram. For scientists in this field, the BS/Orl and BR/Orl mouse lines, derived from a genetic selection, constitute an original mouse model "in mirror" of absence epilepsy. The potential of MALDI imaging mass spectrometry (IMS) for the discovery of potential biomarkers is increasingly recognized. Interestingly, statistical analysis tools specifically adapted to IMS data sets and methods for the identification of detected proteins play an essential role. In this study, a new cross-classification comparative design using a combined discrete wavelet transformation-support vector machine classification was developed to discriminate spectra of brain sections of BS/Orl and BR/Orl mice. Nineteen m/z ratios were thus highlighted as potential markers with very high recognition rates (87-99%). Seven of these potential markers were identified using a top-down approach, in particular a fragment of Synapsin-I. This protein is yet suspected to be involved in epilepsy. Immunohistochemistry and Western Blot experiments confirmed the differential expression of Synapsin-I observed by IMS, thus tending to validate our approach. Functional assays are being performed to confirm the involvement of Synapsin-I in the mechanisms underlying childhood absence epilepsy.
ISSN: 1535-3893

hal-00877728
https://hal.archives-ouvertes.fr/hal-00877728
DOI : 10.1021/pr3006974
PUBMED : 22994238

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
With the growing use of selective serotonin reuptake inhibitor medications (SSRIs) for the treatment of depression during the perinatal period, questions have been raised about the longterm impact of these medications on development. We aimed to investigate how developmental SSRI exposure may alter affect-related behaviors and associated molecular processes in offspring using a rodent model of maternal stress and depression. For this purpose, prenatally stressed or non-stressed male offspring were exposed to fluoxetine (5 mg/kg/day) or vehicle, via lactation, until weaning. Primary results show that postnatal fluoxetine exposure differentially altered anxiety-like behavior by increasing anxiety in non-stressed offspring and decreasing anxiety in prenatally stressed offspring. In the hippocampus, developmental fluoxetine exposure decreased BDNF IV and TrkB mRNA expression. Prenatal stress alone also decreased escape behaviors and decreased hippocampal BDNF IV mRNA expression. These data provide important evidence for the long-term programming effects of early-life exposure to SSRIs on brain and behavior.
ISSN: 0012-1630

hal-01305478
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01305478
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01305478/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01305478/file/Developmental%20SSRIs%2C%20anxiety%20and%20BDNF_accepted.pdf
DOI : 10.1002/dev.21385

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Glioblastoma (GB), the most frequent primary tumor of the central nervous system, remains one of the most lethal human cancers despite intensive researches. Current paradigm in the study of GB has been focused on inter-patient variability and on trying to isolate new classification elements or prognostic factors. Here, using ICPL, a technique for protein relative quantification by mass spectrometry, we investigated protein expression between the four regions of GB on clinically relevant biopsies from 5 patients. We identified 584 non-redundant proteins and 31 proteins were found to be up-regulated in the tumor region compared to the peri-tumoral brain tissue, among which, 24 proteins belong to an interaction network linked to 4 biological processes. The core of this network is mainly constituted of interactions between beta-actin (ACTB) with heat shock proteins (HSP90AA1, HSPA8) and 14-3-3 proteins (YWHAZ, YWHAG, YWHAB). A cluster of three isoforms of the sodium pump α-subunit (ATP1A1, ATP1A2, ATP1A3) was also identified outside this network. The differential expression observed for ACTB and 14-3-3γ was further validated by western blot and/or immunohistochemistry. Our study confirms the identity of previously proposed molecular targets, highlights several functional processes altered in GB such as energy metabolism and synaptic transmission and could thus provide added value to new therapeutic trails.
ISSN: 1874-3919

hal-00877756
https://hal.archives-ouvertes.fr/hal-00877756
DOI : 10.1016/j.jprot.2012.04.034
PUBMED : 22575386

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
The objective of the study was to evaluate the distribution of methotrexate (MTX) in cerebrospinal fluid (CSF) lateral ventricles and in cisterna magna after 3rd intraventricular CSF administration in a rabbit model.MTX or gadolinium chelate (Gd-DOTA) was administered in the 3rd ventricle with a local microdialysis to study the pharmacokinetics at the site of administration and with a simultaneous magnetic resonance imaging (MRI) acquisition in the 3rd ventricle, the lateral ventricles and in the cisterna magna. A specific CSF Physiologically Based Pharmacokinetic (PBPK) model was then extrapolated for MTX from Gd-DOTA data.The relative contribution of elimination and distribution processes to the overall disposition of MTX and Gd-DOTA in the 3rd ventricle was similar (i.e., around 60% for CLE and 40% for CLI) suggesting that Gd-DOTA was a suitable surrogate marker for MTX disposition in ventricular CSF. The PBPK predictions for MTX both in CSF of the 3rd ventricle and in plasma were in accordance with the in vivo results.The present study showed that the combination of local CSF microdialysis with MRI acquisition of the brain ventricles and a PBPK model could be a useful methodology to estimate the drug diffusion within CSF ventricles after direct brain CSF administration. Such a methodology would be of interest to clinicians for a rationale determination and optimization of drug dosing parameters in the treatment of leptomeningeal metastases.
ISSN: 0939-6411

hal-01335562
https://hal.archives-ouvertes.fr/hal-01335562
https://hal.archives-ouvertes.fr/hal-01335562/document
https://hal.archives-ouvertes.fr/hal-01335562/file/PBPK%20model%20of%20methotrexate%20in%20cerebrospinal%20fluid.pdf
DOI : 10.1016/j.ejpb.2016.04.012

Éditeur(s) : HAL CCSD Frontiers
Résumé : International audience
Estrogens can induce rapid, short-lived physiological and behavioral responses, in addition to their slow, but long-term, effects at the transcriptional level. To be functionally relevant, these effects should be associated with rapid modulations of estrogens concentrations. 17β-estradiol is synthesized by the enzyme aromatase, using testosterone as a substrate, but can also be degraded into catechol-estrogens via hydroxylation by the same enzyme, leading to an increase or decrease in estrogens concentration, respectively. The first evidence that aromatase activity (AA) can be rapidly modulated came from experiments performed in Japanese quail hypothalamus homogenates. This rapid modulation is triggered by calcium-dependent phosphorylations and was confirmed in other tissues and species. The mechanisms controlling the phosphorylation status, the targeted amino acid residues and the reversibility seem to vary depending of the tissues and is discussed in this review. We currently do not know whether the phosphorylation of the same amino acid affects both aromatase and/or hydroxylase activities or whether these residues are different. These processes provide a new general mechanism by which local estrogen concentration can be rapidly altered in the brain and other tissues.
ISSN: 1662-4548

Droits : http://creativecommons.org/licenses/by/
hal-01142062
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01142062
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01142062/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01142062/file/fnins-09-00083.pdf
PUBMED : 25852459

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
Selective serotonin reuptake inhibitor medication exposure during the perinatal period can have a long term impact in adult offspring on neuroplasticity and the serotonergic system, but the impact of these medications during early development is poorly understood. The aim of this study was to determine the effects of developmental exposure to the SSRI, fluoxetine, on the serotonergic system, dopaminergic system, and synaptophysin density in the prefrontal cortex and hippocampus, as well as number of immature neurons in the dentate gyrus, in juvenile rat offspring at weaning. To model aspects of maternal depression, prenatal restraint stress was used. Sprague-Dawley rat offspring were exposed to either prenatal stress and/or fluoxetine. Main findings show that developmental fluoxetine exposure to prenatally stressed offspring decreased 5-HT and 5-HIAA levels and altered the dopaminergic system in the hippocampus. Prenatal stress, regardless of fluoxetine, increased synaptophysin density in the PFC. This work indicates that early exposure to maternal stress and SSRI medication can alter brain monoamine levels and synaptophysin density in offspring at weaning. © 2015 Wiley Periodicals, Inc. Dev Psychobiol
ISSN: 0012-1630

hal-01237091
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01237091
DOI : 10.1002/dev.21372
PUBMED : 26477449

Éditeur(s) : HAL CCSD
Résumé : International audience
MOTIVATION: Imaging mass spectrometry (IMS) is a maturating technique of molecular imaging. Confidence in the reproducible quality of IMS data is essential for its integration into routine use. However, the predominant method for assessing quality is visual examination, a time consuming, unstandardized and non-scalable approach. So far, the problem of assessing the quality has only been marginally addressed and existing measures do not account for the spatial information of IMS data. Importantly, no approach exists for unbiased evaluation of potential quality measures. RESULTS: We propose a novel approach for evaluating potential measures by creating a gold-standard set using collective expert judgements upon which we evaluated image-based measures. To produce a gold standard, we engaged 80 IMS experts, each to rate the relative quality between 52 pairs of ion images from MALDI-TOF IMS datasets of rat brain coronal sections. Experts' optional feedback on their expertise, the task and the survey showed that (i) they had diverse backgrounds and sufficient expertise, (ii) the task was properly understood, and (iii) the survey was comprehensible. A moderate inter-rater agreement was achieved with Krippendorff's alpha of 0.5. A gold-standard set of 634 pairs of images with accompanying ratings was constructed and showed a high agreement of 0.85. Eight families of potential measures with a range of parameters and statistical descriptors, giving 143 in total, were evaluated. Both signal-to-noise and spatial chaos-based measures performed highly with a correlation of 0.7 to 0.9 with the gold standard ratings. Moreover, we showed that a composite measure with the linear coefficients (trained on the gold standard with regularized least squares optimization and lasso) showed a strong linear correlation of 0.94 and an accuracy of 0.98 in predicting which image in a pair was of higher quality. AVAILABILITY AND IMPLEMENTATION: The anonymized data collected from the survey and the Matlab source code for data processing can be found at: https://github.com/alexandrovteam/IMS_quality. CONTACT: theodore.alexandrov@embl.de
Bioinformatics (Oxford, England)

hal-01163754
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01163754
DOI : 10.1093/bioinformatics/btv266
PUBMED : 26072506