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Sex Hormones Regulate SHANK Expression
Autism spectrum disorders (ASD) have a higher prevalence in male individuals compared to females, with a ratio of affected boys compared to girls of 4:1 for ASD and 11:1 for Asperger syndrome. Mutations in the SHANK genes (comprising SHANK1, SHANK2 and SHANK3) coding for postsynaptic scaffolding pro...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6167484/ https://www.ncbi.nlm.nih.gov/pubmed/30319350 http://dx.doi.org/10.3389/fnmol.2018.00337 |
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author | Berkel, Simone Eltokhi, Ahmed Fröhlich, Henning Porras-Gonzalez, Diana Rafiullah, Rafiullah Sprengel, Rolf Rappold, Gudrun A. |
author_facet | Berkel, Simone Eltokhi, Ahmed Fröhlich, Henning Porras-Gonzalez, Diana Rafiullah, Rafiullah Sprengel, Rolf Rappold, Gudrun A. |
author_sort | Berkel, Simone |
collection | PubMed |
description | Autism spectrum disorders (ASD) have a higher prevalence in male individuals compared to females, with a ratio of affected boys compared to girls of 4:1 for ASD and 11:1 for Asperger syndrome. Mutations in the SHANK genes (comprising SHANK1, SHANK2 and SHANK3) coding for postsynaptic scaffolding proteins have been tightly associated with ASD. As early brain development is strongly influenced by sex hormones, we investigated the effect of dihydrotestosterone (DHT) and 17β-estradiol on SHANK expression in a human neuroblastoma cell model. Both sex hormones had a significant impact on the expression of all three SHANK genes, which could be effectively blocked by androgen and estrogen receptor antagonists. In neuron-specific androgen receptor knock-out mice (Ar(NesCre)), we found a nominal significant reduction of all Shank genes at postnatal day 7.5 in the cortex. In the developing cortex of wild-type (WT) CD1 mice, a sex-differential protein expression was identified for all Shanks at embryonic day 17.5 and postnatal day 7.5 with significantly higher protein levels in male compared to female mice. Together, we could show that SHANK expression is influenced by sex hormones leading to a sex-differential expression, thus providing novel insights into the sex bias in ASD. |
format | Online Article Text |
id | pubmed-6167484 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-61674842018-10-12 Sex Hormones Regulate SHANK Expression Berkel, Simone Eltokhi, Ahmed Fröhlich, Henning Porras-Gonzalez, Diana Rafiullah, Rafiullah Sprengel, Rolf Rappold, Gudrun A. Front Mol Neurosci Neuroscience Autism spectrum disorders (ASD) have a higher prevalence in male individuals compared to females, with a ratio of affected boys compared to girls of 4:1 for ASD and 11:1 for Asperger syndrome. Mutations in the SHANK genes (comprising SHANK1, SHANK2 and SHANK3) coding for postsynaptic scaffolding proteins have been tightly associated with ASD. As early brain development is strongly influenced by sex hormones, we investigated the effect of dihydrotestosterone (DHT) and 17β-estradiol on SHANK expression in a human neuroblastoma cell model. Both sex hormones had a significant impact on the expression of all three SHANK genes, which could be effectively blocked by androgen and estrogen receptor antagonists. In neuron-specific androgen receptor knock-out mice (Ar(NesCre)), we found a nominal significant reduction of all Shank genes at postnatal day 7.5 in the cortex. In the developing cortex of wild-type (WT) CD1 mice, a sex-differential protein expression was identified for all Shanks at embryonic day 17.5 and postnatal day 7.5 with significantly higher protein levels in male compared to female mice. Together, we could show that SHANK expression is influenced by sex hormones leading to a sex-differential expression, thus providing novel insights into the sex bias in ASD. Frontiers Media S.A. 2018-09-25 /pmc/articles/PMC6167484/ /pubmed/30319350 http://dx.doi.org/10.3389/fnmol.2018.00337 Text en Copyright © 2018 Berkel, Eltokhi, Fröehlich, Porras-Gonzalez, Rafiullah, Sprengel and Rappold. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience Berkel, Simone Eltokhi, Ahmed Fröhlich, Henning Porras-Gonzalez, Diana Rafiullah, Rafiullah Sprengel, Rolf Rappold, Gudrun A. Sex Hormones Regulate SHANK Expression |
title | Sex Hormones Regulate SHANK Expression |
title_full | Sex Hormones Regulate SHANK Expression |
title_fullStr | Sex Hormones Regulate SHANK Expression |
title_full_unstemmed | Sex Hormones Regulate SHANK Expression |
title_short | Sex Hormones Regulate SHANK Expression |
title_sort | sex hormones regulate shank expression |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6167484/ https://www.ncbi.nlm.nih.gov/pubmed/30319350 http://dx.doi.org/10.3389/fnmol.2018.00337 |
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