Docosahexaenoic Acid and Melatonin Prevent Impaired Oligodendrogenesis Induced by Intrauterine Growth Restriction (IUGR)
Por:
Kühne BA, Vázquez-Aristizabal P, Fuentes-Amell M, Pla-Codina L, Loreiro C, Gómez-Catalán J, Gratacós E, Illa-Armengol M and Barenys M
Publicada:
1 may 2022
Ahead of Print:
23 may 2022
Resumen:
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.
Filiaciones:
:
Grup de Recerca en Toxicologia (GRET), INSA-UB and Toxicology Unit, Pharmacology, Toxicology and Therapeutical Chemistry Department, Faculty of Pharmacy, University of Barcelona, 08028 Barcelona, Spain
BCNatal | Fetal Medicine Research Center (Hospital Clínic and Hospital Sant Joan de Déu), Universitat de Barcelona, 08028 Barcelona, Spain
:
Grup de Recerca en Toxicologia (GRET), INSA-UB and Toxicology Unit, Pharmacology, Toxicology and Therapeutical Chemistry Department, Faculty of Pharmacy, University of Barcelona, 08028 Barcelona, Spain
BCNatal | Fetal Medicine Research Center (Hospital Clínic and Hospital Sant Joan de Déu), Universitat de Barcelona, 08028 Barcelona, Spain
Fuentes-Amell M:
Grup de Recerca en Toxicologia (GRET), INSA-UB and Toxicology Unit, Pharmacology, Toxicology and Therapeutical Chemistry Department, Faculty of Pharmacy, University of Barcelona, 08028 Barcelona, Spain
BCNatal | Fetal Medicine Research Center (Hospital Clínic and Hospital Sant Joan de Déu), Universitat de Barcelona, 08028 Barcelona, Spain
Pla-Codina L:
BCNatal | Fetal Medicine Research Center (Hospital Clínic and Hospital Sant Joan de Déu), Universitat de Barcelona, 08028 Barcelona, Spain
:
BCNatal | Fetal Medicine Research Center (Hospital Clínic and Hospital Sant Joan de Déu), Universitat de Barcelona, 08028 Barcelona, Spain
Institut d'Investigacions Biomèdiques August Pí i Sunyer (IDIBAPS), 08036 Barcelona, Spain
Gómez-Catalán J:
Grup de Recerca en Toxicologia (GRET), INSA-UB and Toxicology Unit, Pharmacology, Toxicology and Therapeutical Chemistry Department, Faculty of Pharmacy, University of Barcelona, 08028 Barcelona, Spain
Gratacós E:
BCNatal | Fetal Medicine Research Center (Hospital Clínic and Hospital Sant Joan de Déu), Universitat de Barcelona, 08028 Barcelona, Spain
Institut d'Investigacions Biomèdiques August Pí i Sunyer (IDIBAPS), 08036 Barcelona, Spain
Center for Biomedical Research on Rare Diseases (CIBER-ER), 08036 Barcelona, Spain
Illa-Armengol M:
BCNatal | Fetal Medicine Research Center (Hospital Clínic and Hospital Sant Joan de Déu), Universitat de Barcelona, 08028 Barcelona, Spain
Institut de Recerca Sant Joan de Déu, 08950 Esplugues de Llobregat, Spain
Barenys M:
Grup de Recerca en Toxicologia (GRET), INSA-UB and Toxicology Unit, Pharmacology, Toxicology and Therapeutical Chemistry Department, Faculty of Pharmacy, University of Barcelona, 08028 Barcelona, Spain
Green Submitted, gold
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