Oligodendrocyte lineage is severely affected in human alcohol-exposed foetuses
Abstract Prenatal alcohol exposure is a major cause of neurobehavioral disabilities. MRI studies in humans have shown that alcohol is associated with white matter microstructural anomalies but these studies focused on myelin abnormalities only after birth. Only one of these studies evaluated oligode...
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| Format: | Article |
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BMC
2022-05-01
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| Series: | Acta Neuropathologica Communications |
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| Online Access: | https://doi.org/10.1186/s40478-022-01378-9 |
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| author | Florent Marguet Mélanie Brosolo Gaëlle Friocourt Fanny Sauvestre Pascale Marcorelles Céline Lesueur Stéphane Marret Bruno J. Gonzalez Annie Laquerrière |
| author_facet | Florent Marguet Mélanie Brosolo Gaëlle Friocourt Fanny Sauvestre Pascale Marcorelles Céline Lesueur Stéphane Marret Bruno J. Gonzalez Annie Laquerrière |
| author_sort | Florent Marguet |
| collection | DOAJ |
| description | Abstract Prenatal alcohol exposure is a major cause of neurobehavioral disabilities. MRI studies in humans have shown that alcohol is associated with white matter microstructural anomalies but these studies focused on myelin abnormalities only after birth. Only one of these studies evaluated oligodendrocyte lineage, but only for a short period during human foetal life. As data are lacking in humans and alcohol is known to impair oligodendrocyte differentiation in rodents, the present study aimed to compare by immunohistochemistry the oligodendrocyte precursor cells expressing PDGFR-α and immature premyelinating/mature oligodendrocytes expressing Olig2 in the ganglionic eminences and the frontal cortex of 14 human foetuses exposed to alcohol from 15 to 37 weeks’ gestation with age-matched controls. The human brains used in this study were obtained at the time of foetal autopsies for medical termination of pregnancy, in utero or post-natal early death. Before birth, PDGFR-α expression was strongly increased in the ganglionic eminences and the cortex of all foetuses exposed to alcohol except at the earliest stage. No massive generation of Olig2 immunoreactive cells was identified in the ganglionic eminences until the end of pregnancy and the density of Olig2-positive cells within the cortex was consistently lower in foetuses exposed to alcohol than in controls. These antenatal data from humans provides further evidence of major oligodendrocyte lineage impairment at specific and key stages of brain development upon prenatal alcohol exposure including defective or delayed generation and maturation of oligodendrocyte precursors. |
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| format | Article |
| id | doaj.art-c6fe454e7389405893008d9f46d22ed9 |
| institution | Directory Open Access Journal |
| issn | 2051-5960 |
| language | English |
| last_indexed | 2024-12-12T05:15:21Z |
| publishDate | 2022-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Acta Neuropathologica Communications |
| spelling | doaj.art-c6fe454e7389405893008d9f46d22ed92022-12-22T00:36:48ZengBMCActa Neuropathologica Communications2051-59602022-05-0110111410.1186/s40478-022-01378-9Oligodendrocyte lineage is severely affected in human alcohol-exposed foetusesFlorent Marguet0Mélanie Brosolo1Gaëlle Friocourt2Fanny Sauvestre3Pascale Marcorelles4Céline Lesueur5Stéphane Marret6Bruno J. Gonzalez7Annie Laquerrière8Department of Pathology, Normandy Centre for Genomic and Personalized Medicine, Laboratoire d’Anatomie Pathologique, Pavillon Jacques Delarue, CHU, Normandie Univ, UNIROUEN, INSERM U1245 and Rouen University HospitalUNIROUEN, INSERM U1245 F76000, Normandy Centre for Genomic and Personalized Medicine, Normandie UnivInserm UMR1078, Université de Bretagne Occidentale, Faculté de Médecine et Des Sciences de la Santé; Etablissement Français du Sang (EFS) Bretagne; Laboratoire de Génétique Moléculaire, CHRU Brest, Hôpital MorvanDepartment of Pathology, Bordeaux University HospitalPathology Laboratory, Pole Pathologie-Biologie, Centre Hospitalier Universitaire BrestUNIROUEN, INSERM U1245 F76000, Normandy Centre for Genomic and Personalized Medicine, Normandie UnivDepartment of Neonatal Paediatrics and Intensive Care, Normandy Centre for Genomic and Personalized Medicine, Normandie Univ, UNIROUEN, INSERM U1245 and Rouen University HospitalUNIROUEN, INSERM U1245 F76000, Normandy Centre for Genomic and Personalized Medicine, Normandie UnivDepartment of Pathology, Normandy Centre for Genomic and Personalized Medicine, Laboratoire d’Anatomie Pathologique, Pavillon Jacques Delarue, CHU, Normandie Univ, UNIROUEN, INSERM U1245 and Rouen University HospitalAbstract Prenatal alcohol exposure is a major cause of neurobehavioral disabilities. MRI studies in humans have shown that alcohol is associated with white matter microstructural anomalies but these studies focused on myelin abnormalities only after birth. Only one of these studies evaluated oligodendrocyte lineage, but only for a short period during human foetal life. As data are lacking in humans and alcohol is known to impair oligodendrocyte differentiation in rodents, the present study aimed to compare by immunohistochemistry the oligodendrocyte precursor cells expressing PDGFR-α and immature premyelinating/mature oligodendrocytes expressing Olig2 in the ganglionic eminences and the frontal cortex of 14 human foetuses exposed to alcohol from 15 to 37 weeks’ gestation with age-matched controls. The human brains used in this study were obtained at the time of foetal autopsies for medical termination of pregnancy, in utero or post-natal early death. Before birth, PDGFR-α expression was strongly increased in the ganglionic eminences and the cortex of all foetuses exposed to alcohol except at the earliest stage. No massive generation of Olig2 immunoreactive cells was identified in the ganglionic eminences until the end of pregnancy and the density of Olig2-positive cells within the cortex was consistently lower in foetuses exposed to alcohol than in controls. These antenatal data from humans provides further evidence of major oligodendrocyte lineage impairment at specific and key stages of brain development upon prenatal alcohol exposure including defective or delayed generation and maturation of oligodendrocyte precursors.https://doi.org/10.1186/s40478-022-01378-9Oligodendrocyte precursorsPDGFR-αOlig2Myelination defectsHuman foetal brainFoetal alcohol syndrome |
| spellingShingle | Florent Marguet Mélanie Brosolo Gaëlle Friocourt Fanny Sauvestre Pascale Marcorelles Céline Lesueur Stéphane Marret Bruno J. Gonzalez Annie Laquerrière Oligodendrocyte lineage is severely affected in human alcohol-exposed foetuses Acta Neuropathologica Communications Oligodendrocyte precursors PDGFR-α Olig2 Myelination defects Human foetal brain Foetal alcohol syndrome |
| title | Oligodendrocyte lineage is severely affected in human alcohol-exposed foetuses |
| title_full | Oligodendrocyte lineage is severely affected in human alcohol-exposed foetuses |
| title_fullStr | Oligodendrocyte lineage is severely affected in human alcohol-exposed foetuses |
| title_full_unstemmed | Oligodendrocyte lineage is severely affected in human alcohol-exposed foetuses |
| title_short | Oligodendrocyte lineage is severely affected in human alcohol-exposed foetuses |
| title_sort | oligodendrocyte lineage is severely affected in human alcohol exposed foetuses |
| topic | Oligodendrocyte precursors PDGFR-α Olig2 Myelination defects Human foetal brain Foetal alcohol syndrome |
| url | https://doi.org/10.1186/s40478-022-01378-9 |
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