Docosahexaenoic Acid and Melatonin Prevent Impaired Oligodendrogenesis Induced by Intrauterine Growth Restriction (IUGR)
In this study, our aims were to characterize oligodendrogenesis alterations in fetuses with intrauterine growth restriction (IUGR) and to find therapeutic strategies to prevent/treat them using a novel rabbit in vitro neurosphere culture. IUGR was surgically induced in one uterine horn of pregnant r...
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MDPI AG
2022-05-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/10/5/1205 |
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| author | Britta Anna Kühne Paula Vázquez-Aristizabal Mercè Fuentes-Amell Laura Pla Carla Loreiro Jesús Gómez-Catalán Eduard Gratacós Miriam Illa Marta Barenys |
| author_facet | Britta Anna Kühne Paula Vázquez-Aristizabal Mercè Fuentes-Amell Laura Pla Carla Loreiro Jesús Gómez-Catalán Eduard Gratacós Miriam Illa Marta Barenys |
| author_sort | Britta Anna Kühne |
| collection | DOAJ |
| description | In this study, our aims were to characterize oligodendrogenesis alterations in fetuses with intrauterine growth restriction (IUGR) and to find therapeutic strategies to prevent/treat them using a novel rabbit in vitro neurosphere culture. IUGR was surgically induced in one uterine horn of pregnant rabbits, while the contralateral horn served as a control. Neural progenitor cells (NPCs) were obtained from pup’s whole brain and cultured as neurospheres mimicking the basic processes of brain development including migration and cell differentiation. Five substances, chosen based on evidence provided in the literature, were screened in vitro in neurospheres from untreated rabbits: Docosahexaenoic acid (DHA), melatonin (MEL), zinc, 3,3′,5-Triiodo-L-thyronine (T3), and lactoferrin (LF) or its metabolite sialic acid (SA). DHA, MEL and LF were further selected for in vivo administration and subsequent evaluation in the Neurosphere Assay. In the IUGR culture, we observed a significantly reduced percentage of oligodendrocytes (OLs) which correlated with clinical findings indicating white matter injury in IUGR infants. We identified DHA and MEL as the most effective therapies. In all cases, our in vitro rabbit neurosphere assay predicted the outcome of the in vivo administration of the therapies and confirmed the reliability of the model, making it a powerful and consistent tool to select new neuroprotective therapies. |
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| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T03:16:38Z |
| publishDate | 2022-05-01 |
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| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-8568f33437da42e3a95fe1b065de0e7a2023-11-23T10:12:34ZengMDPI AGBiomedicines2227-90592022-05-01105120510.3390/biomedicines10051205Docosahexaenoic Acid and Melatonin Prevent Impaired Oligodendrogenesis Induced by Intrauterine Growth Restriction (IUGR)Britta Anna Kühne0Paula Vázquez-Aristizabal1Mercè Fuentes-Amell2Laura Pla3Carla Loreiro4Jesús Gómez-Catalán5Eduard Gratacós6Miriam Illa7Marta Barenys8Grup de Recerca en Toxicologia (GRET), INSA-UB and Toxicology Unit, Pharmacology, Toxicology and Therapeutical Chemistry Department, Faculty of Pharmacy, University of Barcelona, 08028 Barcelona, SpainGrup de Recerca en Toxicologia (GRET), INSA-UB and Toxicology Unit, Pharmacology, Toxicology and Therapeutical Chemistry Department, Faculty of Pharmacy, University of Barcelona, 08028 Barcelona, SpainGrup de Recerca en Toxicologia (GRET), INSA-UB and Toxicology Unit, Pharmacology, Toxicology and Therapeutical Chemistry Department, Faculty of Pharmacy, University of Barcelona, 08028 Barcelona, SpainBCNatal | Fetal Medicine Research Center (Hospital Clínic and Hospital Sant Joan de Déu), Universitat de Barcelona, 08028 Barcelona, SpainBCNatal | Fetal Medicine Research Center (Hospital Clínic and Hospital Sant Joan de Déu), Universitat de Barcelona, 08028 Barcelona, SpainGrup de Recerca en Toxicologia (GRET), INSA-UB and Toxicology Unit, Pharmacology, Toxicology and Therapeutical Chemistry Department, Faculty of Pharmacy, University of Barcelona, 08028 Barcelona, SpainBCNatal | Fetal Medicine Research Center (Hospital Clínic and Hospital Sant Joan de Déu), Universitat de Barcelona, 08028 Barcelona, SpainBCNatal | Fetal Medicine Research Center (Hospital Clínic and Hospital Sant Joan de Déu), Universitat de Barcelona, 08028 Barcelona, SpainGrup de Recerca en Toxicologia (GRET), INSA-UB and Toxicology Unit, Pharmacology, Toxicology and Therapeutical Chemistry Department, Faculty of Pharmacy, University of Barcelona, 08028 Barcelona, SpainIn this study, our aims were to characterize oligodendrogenesis alterations in fetuses with intrauterine growth restriction (IUGR) and to find therapeutic strategies to prevent/treat them using a novel rabbit in vitro neurosphere culture. IUGR was surgically induced in one uterine horn of pregnant rabbits, while the contralateral horn served as a control. Neural progenitor cells (NPCs) were obtained from pup’s whole brain and cultured as neurospheres mimicking the basic processes of brain development including migration and cell differentiation. Five substances, chosen based on evidence provided in the literature, were screened in vitro in neurospheres from untreated rabbits: Docosahexaenoic acid (DHA), melatonin (MEL), zinc, 3,3′,5-Triiodo-L-thyronine (T3), and lactoferrin (LF) or its metabolite sialic acid (SA). DHA, MEL and LF were further selected for in vivo administration and subsequent evaluation in the Neurosphere Assay. In the IUGR culture, we observed a significantly reduced percentage of oligodendrocytes (OLs) which correlated with clinical findings indicating white matter injury in IUGR infants. We identified DHA and MEL as the most effective therapies. In all cases, our in vitro rabbit neurosphere assay predicted the outcome of the in vivo administration of the therapies and confirmed the reliability of the model, making it a powerful and consistent tool to select new neuroprotective therapies.https://www.mdpi.com/2227-9059/10/5/1205progenitor cellscell culturedifferentiationoligodendrocytesnervous system developmentneurogenesis |
| spellingShingle | Britta Anna Kühne Paula Vázquez-Aristizabal Mercè Fuentes-Amell Laura Pla Carla Loreiro Jesús Gómez-Catalán Eduard Gratacós Miriam Illa Marta Barenys Docosahexaenoic Acid and Melatonin Prevent Impaired Oligodendrogenesis Induced by Intrauterine Growth Restriction (IUGR) Biomedicines progenitor cells cell culture differentiation oligodendrocytes nervous system development neurogenesis |
| title | Docosahexaenoic Acid and Melatonin Prevent Impaired Oligodendrogenesis Induced by Intrauterine Growth Restriction (IUGR) |
| title_full | Docosahexaenoic Acid and Melatonin Prevent Impaired Oligodendrogenesis Induced by Intrauterine Growth Restriction (IUGR) |
| title_fullStr | Docosahexaenoic Acid and Melatonin Prevent Impaired Oligodendrogenesis Induced by Intrauterine Growth Restriction (IUGR) |
| title_full_unstemmed | Docosahexaenoic Acid and Melatonin Prevent Impaired Oligodendrogenesis Induced by Intrauterine Growth Restriction (IUGR) |
| title_short | Docosahexaenoic Acid and Melatonin Prevent Impaired Oligodendrogenesis Induced by Intrauterine Growth Restriction (IUGR) |
| title_sort | docosahexaenoic acid and melatonin prevent impaired oligodendrogenesis induced by intrauterine growth restriction iugr |
| topic | progenitor cells cell culture differentiation oligodendrocytes nervous system development neurogenesis |
| url | https://www.mdpi.com/2227-9059/10/5/1205 |
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