Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Maternal affective disorders are frequently treated with selective serotonin reuptake inhibitor medications (SSRIs); with up to 10% of women being prescribed these medications during pregnancy. Infant development depends on the early serotonergic environment, which is altered by perinatal SSRIs, raising concern about how these medications affect neural outcomes. While clinical and preclinical research suggests an impact of SSRIs on the developing brain, more research is needed to determine the effects on neuroplasticity, the serotonergic system, and the hypothalamic-pituitary-adrenal axis in neural regions mediating behavior. The current work investigated the effects of the SSRI, fluoxetine, on the serotonergic system in the prefrontal cortex (PFC) during pre-adolescence, and changes to synaptic markers and glucocorticoid receptor density in the cingulate cortex (medial PFC) of pre-adolescent and adult Sprague-Dawley male and female rats. To model aspects of Perinatal Depression and maternal anxiety, pre-gestational maternal stress was used resulting in male and female offspring from 4 groups: 1) control, 2) perinatal fluoxetine exposed, 3) pre-gestational maternal stress exposed, and 4) pre-gestational maternal stress + fluoxetine. Perinatal fluoxetine prevented the effects of maternal stress on 5-HT levels and 5-HT turnover ratio in the PFC of pre-adolescent offspring, particularly in females. However, pre-gestational stress reduced synaptophysin and PSD-95 densities in the cingulate cortex, effects that were more pronounced in males. Interestingly, perinatal fluoxetine exposure reduced GR density in adult males in this same brain area. Together, results show differential effects of perinatal SSRIs and pre-gestational maternal stress on neurodevelopment in the PFC of males and females.
ISSN: 0028-3908

hal-01647158
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01647158
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01647158/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01647158/file/Gemmel%20-%20Perinatal%20fluoxetine%20prevents%20the%20effect.pdf
DOI : 10.1016/j.neuropharm.2017.10.009

Éditeur(s) : HAL CCSD
Résumé : International audience
Migration of chemicals from packaging materials to foods may lead to human exposure. Polyfluoroalkyl substances (PFAS) can be used in technical mixtures (TMs) for use in food packaging of paper and board, and PFAS have been detected in human serum and umbilical cord blood. The specific structures of the PFAS in TMs are often unknown, but polyfluorinated alkyl phosphate esters (PAPs) have been characterized in TMs, food packaging, and in food. PAPs can be metabolized into fluorotelomer alcohols (FTOHs) and perfluoroalkyl carboxylic acids (PFCAs). Some PFAS have endocrine activities, highlighting the need to investigate these effects. Herein, we studied the endocrine activity of less characterized PFAS, including short-chain PFCAs and FTOHs, PAPs, and TMs of unknown chemical composition. Long-chain PFCAs were also included. We applied seven assays covering effects on estrogen, glucocorticoid, androgen, and peroxisome proliferator-activated receptor (PPAR) activity, as well as steroidogenesis in vitro and ex vivo. In general, PAPs, FTOHs, TMs, and long-chain PFCAs showed estrogenic activity through receptor activation and/or increasing 17β-estradiol levels. Furthermore, short- and long-chain PFCAs activated PPARα and PPARγ. Collectively, this means that (i) PAPs, FTOHs, and PFCAs exhibit endocrine activity through distinct and sometimes different mechanisms, (ii) two out of three tested TMs exhibited estrogenic activity, and (iii) short-chain FTOHs showed estrogenic activity and short-chain PFCAs generally activate both PPARα and PPARγ with similar potency and efficacy as long-chain PFCAs. In conclusion, several new and divergent toxicological targets were identified for different groups of PFAS. © 2016 American Society of Andrology and European Academy of Andrology
Andrology

hal-01367144
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01367144
DOI : 10.1111/andr.12190
PUBMED : 27152447

Éditeur(s) : HAL CCSD Elsevier
Résumé : This manuscript is an extended version, including an updated bibliography, of the article: Hierarchical cooperativity mediated by chromatin remodeling; the model of the MMTV transcription regulation. Michel, D. 2011. J. Theor. Biol. 287, 74-81
International audience
Chromatin remodeling machineries are abundant and diverse in eukaryotic cells. They have been involved in a variety of situations such as histone exchange and DNA repair, but their importance in gene expression remains unclear. Although the influence of nucleosome position on the regulation of gene expression is generally envisioned under the quasi-equilibrium perspective, it is proposed that given the ATP-dependence of chro-matin remodeling enzymes, certain mechanisms necessitate non-equilibrium treatments. Examination of the celebrated chromatin remodeling system of the mouse mammary tumor virus, in which the binding of transcription factors opens the way to other ones, reveals that breaking equilibrium offers a subtle mode of transcription factor cooperativity, avoids molecular trapping phenomena and allows to reconcile previously conflicting experimental data. This mechanism provides a control lever of promoter responsiveness to transcription factor combinations, challenging the classical view of the unilateral influence of pioneer on secondary transcription factors.
ISSN: 0022-5193

hal-01211233
https://hal.archives-ouvertes.fr/hal-01211233
https://hal.archives-ouvertes.fr/hal-01211233/document
https://hal.archives-ouvertes.fr/hal-01211233/file/nucleosome.pdf
ARXIV : 1509.07440