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Neurogenesis of Subventricular Zone Progenitors in the Premature Cortex of Ferrets Facilitated by Neonatal Valproic Acid Exposure
The present study evaluated the neurogenesis of neonatal valproic acid (VPA) exposure on subventricular zone progenitors of the developing cerebral cortex in ferrets. VPA was injected at a dose of 200 µg/g of body weight into ferret infants on postnatal days 6 and 7. Two different thymidine analogue...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9099828/ https://www.ncbi.nlm.nih.gov/pubmed/35563273 http://dx.doi.org/10.3390/ijms23094882 |
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author | Sawada, Kazuhiko |
author_facet | Sawada, Kazuhiko |
author_sort | Sawada, Kazuhiko |
collection | PubMed |
description | The present study evaluated the neurogenesis of neonatal valproic acid (VPA) exposure on subventricular zone progenitors of the developing cerebral cortex in ferrets. VPA was injected at a dose of 200 µg/g of body weight into ferret infants on postnatal days 6 and 7. Two different thymidine analogues, 5-ethynyl-2′-deoxyuridine (EdU) and 5-bromo-2′-deoxyuridine (BrdU), were injected with a 48 h interval to label proliferating cells before and after VPA exposure. Two hours after BrdU injection, BrdU single- and EdU/BrdU double-labeled cells, but not EdU single-labeled cells, were significantly denser in both the inner and outer subventricular zones of VPA-exposed infants than in control infants. Notably, more than 97% of BrdU single- and EdU/BrdU double-labeled cells were immunopositive for Pax6, a stable marker for basal radial glia (bRG), in both groups. In contrast, the percentage of cells positively immunostained for Cux1, a postmitotic marker for upper-layer cortical neurons, in both EdU single- and BrdU single-labeled cells, was significantly higher in VPA-exposed infants than in control infants. These findings suggest that neonatal VPA exposure facilitates bRG proliferation, including self-renewal, followed by their differentiation into upper layer cortical neurons in the premature cortex of ferrets. |
format | Online Article Text |
id | pubmed-9099828 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-90998282022-05-14 Neurogenesis of Subventricular Zone Progenitors in the Premature Cortex of Ferrets Facilitated by Neonatal Valproic Acid Exposure Sawada, Kazuhiko Int J Mol Sci Article The present study evaluated the neurogenesis of neonatal valproic acid (VPA) exposure on subventricular zone progenitors of the developing cerebral cortex in ferrets. VPA was injected at a dose of 200 µg/g of body weight into ferret infants on postnatal days 6 and 7. Two different thymidine analogues, 5-ethynyl-2′-deoxyuridine (EdU) and 5-bromo-2′-deoxyuridine (BrdU), were injected with a 48 h interval to label proliferating cells before and after VPA exposure. Two hours after BrdU injection, BrdU single- and EdU/BrdU double-labeled cells, but not EdU single-labeled cells, were significantly denser in both the inner and outer subventricular zones of VPA-exposed infants than in control infants. Notably, more than 97% of BrdU single- and EdU/BrdU double-labeled cells were immunopositive for Pax6, a stable marker for basal radial glia (bRG), in both groups. In contrast, the percentage of cells positively immunostained for Cux1, a postmitotic marker for upper-layer cortical neurons, in both EdU single- and BrdU single-labeled cells, was significantly higher in VPA-exposed infants than in control infants. These findings suggest that neonatal VPA exposure facilitates bRG proliferation, including self-renewal, followed by their differentiation into upper layer cortical neurons in the premature cortex of ferrets. MDPI 2022-04-28 /pmc/articles/PMC9099828/ /pubmed/35563273 http://dx.doi.org/10.3390/ijms23094882 Text en © 2022 by the author. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Sawada, Kazuhiko Neurogenesis of Subventricular Zone Progenitors in the Premature Cortex of Ferrets Facilitated by Neonatal Valproic Acid Exposure |
title | Neurogenesis of Subventricular Zone Progenitors in the Premature Cortex of Ferrets Facilitated by Neonatal Valproic Acid Exposure |
title_full | Neurogenesis of Subventricular Zone Progenitors in the Premature Cortex of Ferrets Facilitated by Neonatal Valproic Acid Exposure |
title_fullStr | Neurogenesis of Subventricular Zone Progenitors in the Premature Cortex of Ferrets Facilitated by Neonatal Valproic Acid Exposure |
title_full_unstemmed | Neurogenesis of Subventricular Zone Progenitors in the Premature Cortex of Ferrets Facilitated by Neonatal Valproic Acid Exposure |
title_short | Neurogenesis of Subventricular Zone Progenitors in the Premature Cortex of Ferrets Facilitated by Neonatal Valproic Acid Exposure |
title_sort | neurogenesis of subventricular zone progenitors in the premature cortex of ferrets facilitated by neonatal valproic acid exposure |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9099828/ https://www.ncbi.nlm.nih.gov/pubmed/35563273 http://dx.doi.org/10.3390/ijms23094882 |
work_keys_str_mv | AT sawadakazuhiko neurogenesisofsubventricularzoneprogenitorsintheprematurecortexofferretsfacilitatedbyneonatalvalproicacidexposure |