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The flavonoid 7,8-DHF fosters prenatal brain proliferation potency in a mouse model of Down syndrome
Neurogenesis impairment is a key determinant of intellectual disability in Down syndrome (DS), a genetic pathology due to triplication of chromosome 21. Since neurogenesis ceases after birth, apart in the hippocampus and olfactory bulb, the only means to tackle the problem of neurogenesis impairment...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973813/ https://www.ncbi.nlm.nih.gov/pubmed/33737521 http://dx.doi.org/10.1038/s41598-021-85284-5 |
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author | Stagni, Fiorenza Uguagliati, Beatrice Emili, Marco Giacomini, Andrea Bartesaghi, Renata Guidi, Sandra |
author_facet | Stagni, Fiorenza Uguagliati, Beatrice Emili, Marco Giacomini, Andrea Bartesaghi, Renata Guidi, Sandra |
author_sort | Stagni, Fiorenza |
collection | PubMed |
description | Neurogenesis impairment is a key determinant of intellectual disability in Down syndrome (DS), a genetic pathology due to triplication of chromosome 21. Since neurogenesis ceases after birth, apart in the hippocampus and olfactory bulb, the only means to tackle the problem of neurogenesis impairment in DS at its root is to intervene during gestation. A few studies in DS mouse models show that this is possible, although the drugs used may raise caveats in terms of safety. We previously found that neonatal treatment with 7,8-dihydroxyflavone (7,8-DHF), a flavonoid present in plants, restores hippocampal neurogenesis in the Ts65Dn model of DS. The goal of the current study was to establish whether prenatal treatment with 7,8-DHF improves/restores overall brain proliferation potency. Pregnant Ts65Dn females received 7,8-DHF from embryonic day 10 until delivery. On postnatal day 2 (P2) the pups were injected with BrdU and were killed after either 2 h or 52–60 days (P52–60). Evaluation of the number of proliferating (BrdU+) cells in various forebrain neurogenic niches of P2 mice showed that in treated Ts65Dn mice proliferation potency was improved or even restored in most of the examined regions, including the hippocampus. Quantification of the surviving BrdU+ cells in the dentate gyrus of P52–60 mice showed no difference between treated and untreated Ts65Dn mice. At P52–60, however, treated Ts65Dn mice exhibited a larger number of granule cells in comparison with their untreated counterparts, although their number did not reach that of euploid mice. Results show that 7,8-DHF has a widespread impact on prenatal proliferation potency in Ts65Dn mice and exerts mild long-term effects. It remains to be established whether treatment extending into the neonatal period can lead to an improvement in brain development that is retained in adulthood. |
format | Online Article Text |
id | pubmed-7973813 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-79738132021-03-19 The flavonoid 7,8-DHF fosters prenatal brain proliferation potency in a mouse model of Down syndrome Stagni, Fiorenza Uguagliati, Beatrice Emili, Marco Giacomini, Andrea Bartesaghi, Renata Guidi, Sandra Sci Rep Article Neurogenesis impairment is a key determinant of intellectual disability in Down syndrome (DS), a genetic pathology due to triplication of chromosome 21. Since neurogenesis ceases after birth, apart in the hippocampus and olfactory bulb, the only means to tackle the problem of neurogenesis impairment in DS at its root is to intervene during gestation. A few studies in DS mouse models show that this is possible, although the drugs used may raise caveats in terms of safety. We previously found that neonatal treatment with 7,8-dihydroxyflavone (7,8-DHF), a flavonoid present in plants, restores hippocampal neurogenesis in the Ts65Dn model of DS. The goal of the current study was to establish whether prenatal treatment with 7,8-DHF improves/restores overall brain proliferation potency. Pregnant Ts65Dn females received 7,8-DHF from embryonic day 10 until delivery. On postnatal day 2 (P2) the pups were injected with BrdU and were killed after either 2 h or 52–60 days (P52–60). Evaluation of the number of proliferating (BrdU+) cells in various forebrain neurogenic niches of P2 mice showed that in treated Ts65Dn mice proliferation potency was improved or even restored in most of the examined regions, including the hippocampus. Quantification of the surviving BrdU+ cells in the dentate gyrus of P52–60 mice showed no difference between treated and untreated Ts65Dn mice. At P52–60, however, treated Ts65Dn mice exhibited a larger number of granule cells in comparison with their untreated counterparts, although their number did not reach that of euploid mice. Results show that 7,8-DHF has a widespread impact on prenatal proliferation potency in Ts65Dn mice and exerts mild long-term effects. It remains to be established whether treatment extending into the neonatal period can lead to an improvement in brain development that is retained in adulthood. Nature Publishing Group UK 2021-03-18 /pmc/articles/PMC7973813/ /pubmed/33737521 http://dx.doi.org/10.1038/s41598-021-85284-5 Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Stagni, Fiorenza Uguagliati, Beatrice Emili, Marco Giacomini, Andrea Bartesaghi, Renata Guidi, Sandra The flavonoid 7,8-DHF fosters prenatal brain proliferation potency in a mouse model of Down syndrome |
title | The flavonoid 7,8-DHF fosters prenatal brain proliferation potency in a mouse model of Down syndrome |
title_full | The flavonoid 7,8-DHF fosters prenatal brain proliferation potency in a mouse model of Down syndrome |
title_fullStr | The flavonoid 7,8-DHF fosters prenatal brain proliferation potency in a mouse model of Down syndrome |
title_full_unstemmed | The flavonoid 7,8-DHF fosters prenatal brain proliferation potency in a mouse model of Down syndrome |
title_short | The flavonoid 7,8-DHF fosters prenatal brain proliferation potency in a mouse model of Down syndrome |
title_sort | flavonoid 7,8-dhf fosters prenatal brain proliferation potency in a mouse model of down syndrome |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973813/ https://www.ncbi.nlm.nih.gov/pubmed/33737521 http://dx.doi.org/10.1038/s41598-021-85284-5 |
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