Neurocentre Magendie



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Depuis 2004: Ingénieur de Recherche, Bordeaux Sciences Agro
2003-2004: Post-doc, INSERM U828 Cardiovasculaire
1998-2002: Instructor of Medicine, Renal Cell Biology, Vascular Biology Institute, University of Miami
1998: PhD Sciences Pharmaceutiques, Université Bordeaux 2, Physiopathologie Rénale

Expertise: Cell Biology, Estrogen Receptor, Hippocampal neurons, Synaptic plasticity

36 publication(s) depuis Décembre 1994:

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Les IF indiqués ont été collectés par le Web of Sciences en

21/03/2016 | Psychoneuroendocrinology   IF 4.2
Estradiol enhances retention but not organization of hippocampus-dependent memory in intact male mice.
Al Abed AS, Sellami A, Brayda-Bruno L, Lamothe V, Nogues X, Potier M, Bennetau-Pelissero C, Marighetto A

Because estrogens have mostly been studied in gonadectomized females, effects of chronic exposure to environmental estrogens in the general population are underestimated. Estrogens can enhance hippocampus-dependent memory through the modulation of information storage. However, declarative memory, the hippocampus-dependent memory of facts and events, demands more than abilities to retain information. Specifically, memory of repetitive events of everyday life such as 'where I parked' requires abilities to organize/update memories to prevent proactive interference from similar memories of previous 'parking events'. Whether such organizational processes are estrogen-sensitive is unknown. We here studied, in intact young and aged adult mice, drinking-water (1muM) estradiol effects on both retention and organizational components of hippocampus-dependent memory, using a radial-maze task of everyday-like memory. Demand on retention vs organization was manipulated by varying the time-interval separating repetitions of similar events. Estradiol increased performance in young and aged mice under minimized organizational demand, but failed to improve the age-associated memory impairment and diminished performance in young mice under high organizational demand. In fact, estradiol prolonged mnemonic retention of successive events without improving organization abilities, hence resulted in more proactive interference from irrelevant memories. c-Fos imaging of testing-induced brain activations showed that the deterioration of young memory was associated with dentate gyrus dysconnectivity, reminiscent of that seen in aged mice. Our findings support the view that estradiol is promnesic but also reveal that such property can paradoxically impair memory. These findings have important outcomes regarding health issues relative to the impact of environmental estrogens in the general population.

31/07/2015 | Biol Psychiatry   IF 8.9
Temporal Memory and Its Enhancement by Estradiol Requires Surface Dynamics of Hippocampal CA1 N-Methyl-D-Aspartate Receptors.
Potier M, Georges F, Brayda-Bruno L, Ladepeche L, Lamothe V, Al Abed AS, Groc L, Marighetto A

BACKGROUND: Identifying the underlying cellular mechanisms of episodic memory is an important challenge, since this memory, based on temporal and contextual associations among events, undergoes preferential degradation in aging and various neuropsychiatric disorders. Memory storage of temporal and contextual associations is known to rely on hippocampal N-methyl-D-aspartate receptor (NMDAR)-dependent synaptic plasticity, which depends ex vivo on dynamic organization of surface NMDARs. Whether NMDAR surface trafficking sustains the formation of associative memory, however, remains unknown. METHODS: We tested this hypothesis, using single nanoparticle imaging, electrophysiology, and behavioral approaches, in hippocampal networks challenged with a potent modulator of NMDAR-dependent synaptic plasticity and memory, 17beta-estradiol (E2). RESULTS: We demonstrate that E2 modulates NMDAR surface trafficking, a necessary condition for E2-induced potentiation at hippocampal cornu ammonis 1 synapses. Strikingly, cornu ammonis 1 NMDAR surface trafficking controls basal and E2-enhanced mnemonic retention of temporal, but not contextual, associations. CONCLUSIONS: NMDAR surface trafficking and its modulation by the sex hormone E2 is a cellular mechanism critical for a major component of episodic memory, opening a new and noncanonical research avenue in the physiopathology of cognition.

05/2012 | J Nutr Biochem   IF 4.7
Naringin, the major grapefruit flavonoid, specifically affects atherosclerosis development in diet-induced hypercholesterolemia in mice.
Chanet A, Milenkovic D, Deval C, Potier M, Constans J, Mazur A, Bennetau-Pelissero C, Morand C, Berard AM

Naringin (NAR) from grapefruit has exhibited potential protective effects against atherosclerosis development. However, specific mechanisms responsible for such effects are poorly understood. Thus, we aimed to investigate the antiatherogenic effects of NAR in different mouse models of hypercholesterolemia and decipher its molecular targets in the aorta using transcriptomic approach. Two mouse models of hypercholesterolemia, wild-type mice fed a high-fat/high-cholesterol diet and apolipoprotein E-deficient mice fed a semisynthetic diet, were studied. Mice were fed a respective control diets supplemented or not for 18 weeks with 0.02% of NAR, that is, nutritional supplementation. NAR supplementation reduced plaque progression only in wild-type mice fed the high-fat/high-cholesterol diet (-41%). Consistent with this protective effect, NAR reduced plasma non-high-density lipoprotein cholesterol concentrations as well as biomarkers of endothelial dysfunction. Microarray studies performed on aortas demonstrated differentially expressed genes encoding proteins involved in cell adhesion, actin cytoskeleton organization and cell division. Thus, the changes in gene expression induced by NAR could suggest a limited atherosclerosis progression by preventing immune cell adhesion and infiltration in the intima of vascular wall, as well as smooth muscle cell proliferation. Furthermore, this hypothesis was strengthened by in vitro experiments, which showed the ability of naringenin to reduce monocyte adhesion to endothelial cells and smooth muscle cell proliferation. In conclusion, this study revealed the antiatherogenic effect of NAR supplemented at a nutritionally achievable dose, specifically toward diet-induced atherosclerosis, and depicted its multitarget mode of action at the vascular level.

Equol, one of the main metabolites of daidzein, is a chiral compound with pleiotropic effects on cellular signaling. This property may induce activation/inhibition of the estrogen receptors (ER) a or b, and therefore, explain the beneficial/deleterious effects of equol on estrogen-dependent diseases. With its asymmetric centre at position C-3, equol can exist in two enantiomeric forms (R- and S-equol). To elucidate the yet unclear mechanisms of ER activation/inhibition by equol, we performed a comprehensive analysis of ERa and ERb transactivation by racemic equol, as well as by enantiomerically pure forms. Racemic equol was prepared by catalytic hydrogenation from daidzein and separated into enantiomers by chiral HPLC. The configuration assignment was performed by optical rotatory power measurements. The ER-induced transactivation by R- and S-equol (0.1-10 microM) and 17b-estradiol (E2, 10 nM) was studied using transient transfections of ERalpha and ERbeta in CHO, HepG2 and HeLa cell lines. R- and S-equol induce ER transactivation in an opposite fashion according to the cellular context. R-equol and S-equol are more potent in inducing ERalpha in an AF-2 and AF-1 permissive cell line, respectively. Involvement of ERalpha transactivation functions (AF-1 and AF-2) in these effects has been examined. Both AF-1 and AF-2 are involved in racemic equol, R-equol and S-equol induced ERalpha transcriptional activity. These results could be of interest to find a specific ligand modulating ER transactivation and could contribute to explaining the diversity of equol actions in vivo.

Estrogens used in hormone replacement therapy regimens may increase the risk of developing breast cancer. Paradoxically, high consumption of plant-derived phytoestrogens, particularly soybean isoflavones, is associated with a low incidence of breast cancer. To explore the molecular basis for these potentially different experimental/clinical outcomes, we investigated whether soybean isoflavones elicit distinct transcriptional actions from estrogens by performing transient transfections in different cell lines. Our results demonstrate that 17beta estradiol (E2), isoflavones, and equol (EQ) effectively trigger the transcriptional activation with both estrogen receptors (ER), ER alpha and ER beta. ER alpha transcriptional activity is mediated through two transactivation domains AF-1 and AF-2, whose activity is tightly regulated in a cell-type and promoter-specific manner. Isoflavones, genistein, and daidzein (DAI), and EQ, the main estrogenic metabolite of DAI, are ER alpha agonists for transcriptional activation. The molecular mechanisms for ER alpha-induced transcriptional activity by isoflavones and EQ involve their capacity to act mainly through AF-1 regardless of the cell type. Therefore, our data indicate that estrogenic ligands, such as isoflavones and EQ, exert their effects on ER alpha transactivation similarly to the endogenous ligand E2, and suggest that the risk of estrogen-related diseases might not be reduced by soy-rich food and/or isoflavone- or EQ-based supplements.

Lignans are plant compounds metabolized in the mammalian gut to produce the estrogenic enterolignans, enterodiol (ED) and enterolactone (EL). Because estrogens have been linked to breast cancer etiology, enterolignans could affect breast cancer risk, but to our knowledge, the mechanisms by which they exert their estrogenic and/or anti-estrogenic effects in humans are still unclear. To better understand how estrogenic compounds from the food, such as the enterolignans, might influence breast cancer progression and their mechanisms to interfere with human estrogen receptor (ER) signalling in hormone-dependant diseases, we examined and compared the ability of ED, EL and 17beta-estradiol (E2) to induce the transactivation of ERalpha and ERbeta, to modulate ERalpha target genes, to exert either growth stimulatory or anti-proliferative effects and finally to modulate MCF-7 cell migration by acting on matrix metalloproteases (MMP)-2 and -9, at concentrations that are achievable through a lignan-rich diet. This study indicates that enterolignans show distinct properties for transactivation of ERalpha and ERbeta. ED, as E2, induces ERalpha transcriptional activation through transactivation functions AF-1 and AF-2, while EL is less efficient in inducing AF-1, acting predominantly through AF-2. Furthermore, ED and EL modulate ERalpha mRNA and protein contents as well as MCF-7 cell proliferation and secreted MMP activities in a different way. Enterolignans are compounds of wide interest nowadays and our results help to unveil their mechanisms of action on ER, emphasizing the fact that the dietary load in lignans could be of importance in the balance between being risk or chemopreventive factors for breast cancer and women's health.

05/2008 | J Clin Endocrinol Metab   IF 6.2
Activation of the estrogen receptor contributes to the progression of pulmonary
Glassberg MK, Elliot SJ, Fritz J, Catanuto P, Potier M, Donahue R, Stetler-Stevenson W, Karl M

CONTEXT: The role of estrogens in the pathogenesis of lymphangioleiomyomatosis

15/02/2008 | Br J Nutr   IF 3.4
Higher bioavailability of isoflavones after a single ingestion of a soya-based supplement than a soya-based food in young healthy males.
Vergne S, Bennetau C, Lamothe V, Chantre P, Potier M, Asselineau J, Perez P, Durand M, Moore N, Sauvant S

Soya isoflavones, genistein and daidzein, are the focus of numerous studies investigating their potential effects on health and results remain controversial. Bioavailability is clearly a crucial factor influencing their bioefficacy and could explain these discrepancies. This study aimed at assessing: (1) the isoflavone content of sixty-nine European soya-derivative products sold on the French market; (2) the bioavailability of isoflavones comparing supplement with food. Twelve healthy volunteers were recruited in a randomized two-way crossover trial and received 35 mg isoflavones equivalent aglycone either through supplements or through cheese, both containing different patterns of isoflavone conjugates and different daidzein:genistein ratios. A specific ELISA method was used to assess the plasma and urinary concentrations of isoflavones and thus the pharmacokinetic parameters, which were then normalized to mg of each isoflavone ingested. Results showed that the normalized Cmax of daidzein (P = 0.002) and similarly the normalized AUC0 --> infinity and Cmax of genistein (P = 0.002) from soya-based capsules were higher than that from soya-based cheese. In conclusion, this work completes studies on isoflavone bioavailability and presents new data regarding isoflavone concentrations in soya-derivative products. Assuming that isoflavone conjugation patterns do not influence isoflavone bioavailability, this study shows that isoflavones contained in capsules are more bioavailable than those contained in soya-based cheese. Although the supplement is more bioavailable, the relative importance of this is difficult to interpret as there is little evidence that supplements are biologically active in human subjects to date and further studies will be necessary for this specific supplement to prove its efficacy.

12/03/2007 | J Pharm Biomed Anal   IF 2.8
Bioavailability and urinary excretion of isoflavones in humans: effects of soy-based supplements formulation and equol production.
Vergne S, Titier K, Bernard V, Asselineau J, Durand M, Lamothe V, Potier M, Perez P, Demotes-Mainard J, Chantre P, Moore N, Bennetau C, Sauvant P

Soy isoflavones (IF) are of particular interest for their possible estrogenic effects on the symptoms of menopause. The bioavailability of IF is clearly a factor influencing their biological activity. The first aim of this study was to elucidate the impact of the matrix process and especially the formulation of soy-based capsules on IF bioavailability. Twelve healthy volunteers were recruited for a randomized, double-blind, two-way crossover trial and received a single dose of the two soy-based formulations, one containing a pure soy standardized extract of IF, and the other containing soy flour in addition to the standardized extract of IF. Using a new and validated ELISA method, we measured the plasma and urinary concentrations of genistein, daidzein and its metabolite equol. Based on European Medicine Evaluation Agency recommendations, the main pharmacokinetic parameters allowed us to demonstrate the bioequivalence of the two formulations, indicating that the presence or absence of soy flour did not alter either the absorption or the elimination of daidzein and genistein. As bioequivalence was demonstrated, we pooled data collected during the two study-periods to address another original issue: Did the ability to produce equol affect the bioavailability of daidzein? We demonstrated that daidzein excretion was significantly lower in equol producers compared with equol non producers over the entire elimination period of the soy IF. This difference disappeared when equol excretion was added to daidzein excretion in equol producers. Our results indicated that the production of equol could partly explain the difference in daidzein bioavailability after IF ingestion.

08/2006 | Kidney Int   IF 7.7
Combined AGE inhibition and ACEi decreases the progression of established
Zheng F, Zeng YJ, Plati AR, Elliot SJ, Berho M, Potier M, Striker LJ, Striker GE

The accumulation of advanced glycation end products (AGE) is a key factor in