Phénotypes cognitifs aberrants et expression de BDNF altérée par l'hippocampe liées à des modifications épigénétiques chez la souris dépourvue de protéine d'échafaudage post-synaptique SHANK1: Implications pour le trouble du spectre de l'autisme

Aperçu: G.M.

L'ensemble des résultats indique que les deletions de Shank1 conduisent à un phénotype cognitif aberrant caractérisé par des déficiences graves dans la mémoire de reconnaissance d'objet et l'augmentation des taux de BDNF hippocampiques, éventuellement à cause de modifications épigénétiques.  

Ce résultat confirme le lien entre TSA et handicap intellectuel, et suggère une régulation épigénétique comme cible thérapeutique potentielle. 

Hippocampus. 2017 May 12. doi: 10.1002/hipo.22741.

Aberrant cognitive phenotypes and altered hippocampal BDNF expression related to epigenetic modifications in mice lacking the post-synaptic scaffolding protein SHANK1: Implications for autism spectrum disorder

Sungur AÖ¹, Jochner MCE¹, Harb H², Kılıç A², Garn H², Schwarting RKW¹, Wöhr M¹.

Author information

1

Behavioral Neuroscience, Experimental and Biological Psychology, Philipps-University of Marburg, Marburg, Germany.

2

Institute of Laboratory Medicine and Pathobiochemistry-Molecular Diagnostics, Philipps-University of Marburg, Marburg, Germany.

Abstract

Autism spectrum disorder (ASD) is a class of neurodevelopmental disorders characterized by persistent deficits in social communication/interaction, together with restricted/repetitive patterns of behavior. ASD is among the most heritable neuropsychiatric conditions, and while available evidence points to a complex set of genetic factors, the SHANK gene family has emerged as one of the most promising candidates. Here, we assessed ASD-related phenotypes with particular emphasis on social behavior and cognition in Shank1 mouse mutants in comparison to heterozygous and wildtype littermate controls across development in both sexes. While social approach behavior was evident in all experimental conditions and social recognition was only mildly affected by genotype, Shank1^-/- null mutant mice were severely impaired in object recognition memory. This effect was particularly prominent in juveniles, not due to impairments in object discrimination, and replicated in independent mouse cohorts. At the neurobiological level, object recognition deficits were paralleled by increased brain-derived neurotrophic factor (BDNF) protein expression in the hippocampus of Shank1^-/- mice; yet BDNF levels did not differ under baseline conditions. We therefore investigated changes in the epigenetic regulation of hippocampal BDNF expression and detected an enrichment of histone H3 acetylation at the Bdnf promoter1 in Shank1^-/- mice, consistent with increased learning-associated BDNF. Together, our findings indicate that Shank1 deletions lead to an aberrant cognitive phenotype characterized by severe impairments in object recognition memory and increased hippocampal BDNF levels, possibly due to epigenetic modifications. This result supports the link between ASD and intellectual disability, and suggests epigenetic regulation as a potential therapeutic target. This article is protected by copyright. All rights reserved.

© 2017 Wiley Periodicals, Inc.

PMID: 28500650

DOI: 10.1002/hipo.22741

Transgenerational effects of prenatal bisphenol A on social recognition

Traduction: G.M.

Horm Behav. 2013 Oct 5. pii: S0018-506X(13)00187-6. doi: 10.1016/j.yhbeh.2013.09.007.

Effets transgénérationels du bisphénol A prénatal sur la reconnaissance sociale

Wolstenholme JT, Goldsby JA, Rissman EF.

Source

Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA 22908.

Abstract

Le bisphénol A (BPA) est un composé artificiel perturbateur du système endocrinien utilisé pour fabriquer des plastiques en polycarbonate.
On le trouve dans les bouteilles en plastique, des garnitures d'aliments en conserve, les récipients thermoformés et autres articles d'usage courant.

Les études épidemiologiques rapportent des correlations entre les niveaus de BPA durant la grossesse et l'activité, l'anxiété et la dépression chez l'enfant.

 

We fed female mice control or BPA-containing diets that produced plasma BPA concentrations similar to concentrations in humans. Females were mated and at birth, pups were fostered to control dams to limit BPA exposure to gestation in the first generation. Sibling pairs were bred to the third generation with no further BPA exposure. 

 

La première (F1) et la troisième (F3) génération de jeunes souris a été testée pour la reconnaissance sociale et en milieu ouvert.

 

Adult F3 mice were tested for olfactory discrimination. 

 

Dans les deux génération, les jeunes souris exposées au BPA montraient de plus hauts niveaux d'investigation que les souris contrôle dans une tâche de reconnaissance sociale.

 

In F3 BPA exposed mice, dishabituation to a novel female was impaired. In the open field, no differences were noted in F1 mice, while in F3, BPA lineage mice were more active than controls. No impairments were detected in F3 mice, all were able to discriminate different male urine pools and urine from water. No sex differences were found in any task. 

Aucune différence entre les sexes n'a été trouvée dans aucune des tâches. 

 

Ces résultats démontrent que l'exposition au BPA pendant la gestation a une longue durée, des effets transgénérationnels sur la reconnaissance sociale et l'activité chez la souris.  

Ces résultats montrent que l'exposition au BPA a des actions transgénérationnels sur le comportement et peut avoir des implications pour les troubles du comportement neurologique de l'homme. 

PMID: 24100195