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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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Autores principales: Stagni, Fiorenza, Uguagliati, Beatrice, Emili, Marco, Giacomini, Andrea, Bartesaghi, Renata, Guidi, Sandra
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
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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.
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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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