The impact of maternal immune activation on embryonic brain development
The adult brain is a complex structure with distinct functional sub-regions, which are generated from an initial pool of neural epithelial cells within the embryo. This transition requires a number of highly coordinated processes, including neurogenesis, i.e., the generation of neurons, and neuronal...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-03-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2023.1146710/full |
| _version_ | 1811159539940065280 |
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| author | Francesca McEwan Jocelyn D. Glazier Reinmar Hager |
| author_facet | Francesca McEwan Jocelyn D. Glazier Reinmar Hager |
| author_sort | Francesca McEwan |
| collection | DOAJ |
| description | The adult brain is a complex structure with distinct functional sub-regions, which are generated from an initial pool of neural epithelial cells within the embryo. This transition requires a number of highly coordinated processes, including neurogenesis, i.e., the generation of neurons, and neuronal migration. These take place during a critical period of development, during which the brain is particularly susceptible to environmental insults. Neurogenesis defects have been associated with the pathogenesis of neurodevelopmental disorders (NDDs), such as autism spectrum disorder and schizophrenia. However, these disorders have highly complex multifactorial etiologies, and hence the underlying mechanisms leading to aberrant neurogenesis continue to be the focus of a significant research effort and have yet to be established. Evidence from epidemiological studies suggests that exposure to maternal infection in utero is a critical risk factor for NDDs. To establish the biological mechanisms linking maternal immune activation (MIA) and altered neurodevelopment, animal models have been developed that allow experimental manipulation and investigation of different developmental stages of brain development following exposure to MIA. Here, we review the changes to embryonic brain development focusing on neurogenesis, neuronal migration and cortical lamination, following MIA. Across published studies, we found evidence for an acute proliferation defect in the embryonic MIA brain, which, in most cases, is linked to an acceleration in neurogenesis, demonstrated by an increased proportion of neurogenic to proliferative divisions. This is accompanied by disrupted cortical lamination, particularly in the density of deep layer neurons, which may be a consequence of the premature neurogenic shift. Although many aspects of the underlying pathways remain unclear, an altered epigenome and mitochondrial dysfunction are likely mechanisms underpinning disrupted neurogenesis in the MIA model. Further research is necessary to delineate the causative pathways responsible for the variation in neurogenesis phenotype following MIA, which are likely due to differences in timing of MIA induction as well as sex-dependent variation. This will help to better understand the underlying pathogenesis of NDDs, and establish therapeutic targets. |
| first_indexed | 2024-04-10T05:43:57Z |
| format | Article |
| id | doaj.art-229cdda3830449e79256fc7ec719dbc1 |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-04-10T05:43:57Z |
| publishDate | 2023-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-229cdda3830449e79256fc7ec719dbc12023-03-06T04:54:29ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2023-03-011710.3389/fnins.2023.11467101146710The impact of maternal immune activation on embryonic brain developmentFrancesca McEwanJocelyn D. GlazierReinmar HagerThe adult brain is a complex structure with distinct functional sub-regions, which are generated from an initial pool of neural epithelial cells within the embryo. This transition requires a number of highly coordinated processes, including neurogenesis, i.e., the generation of neurons, and neuronal migration. These take place during a critical period of development, during which the brain is particularly susceptible to environmental insults. Neurogenesis defects have been associated with the pathogenesis of neurodevelopmental disorders (NDDs), such as autism spectrum disorder and schizophrenia. However, these disorders have highly complex multifactorial etiologies, and hence the underlying mechanisms leading to aberrant neurogenesis continue to be the focus of a significant research effort and have yet to be established. Evidence from epidemiological studies suggests that exposure to maternal infection in utero is a critical risk factor for NDDs. To establish the biological mechanisms linking maternal immune activation (MIA) and altered neurodevelopment, animal models have been developed that allow experimental manipulation and investigation of different developmental stages of brain development following exposure to MIA. Here, we review the changes to embryonic brain development focusing on neurogenesis, neuronal migration and cortical lamination, following MIA. Across published studies, we found evidence for an acute proliferation defect in the embryonic MIA brain, which, in most cases, is linked to an acceleration in neurogenesis, demonstrated by an increased proportion of neurogenic to proliferative divisions. This is accompanied by disrupted cortical lamination, particularly in the density of deep layer neurons, which may be a consequence of the premature neurogenic shift. Although many aspects of the underlying pathways remain unclear, an altered epigenome and mitochondrial dysfunction are likely mechanisms underpinning disrupted neurogenesis in the MIA model. Further research is necessary to delineate the causative pathways responsible for the variation in neurogenesis phenotype following MIA, which are likely due to differences in timing of MIA induction as well as sex-dependent variation. This will help to better understand the underlying pathogenesis of NDDs, and establish therapeutic targets.https://www.frontiersin.org/articles/10.3389/fnins.2023.1146710/fullmaternal immune activationneurogenesisneurodevelopmentproliferationschizophreniaautism spectrum disorder |
| spellingShingle | Francesca McEwan Jocelyn D. Glazier Reinmar Hager The impact of maternal immune activation on embryonic brain development Frontiers in Neuroscience maternal immune activation neurogenesis neurodevelopment proliferation schizophrenia autism spectrum disorder |
| title | The impact of maternal immune activation on embryonic brain development |
| title_full | The impact of maternal immune activation on embryonic brain development |
| title_fullStr | The impact of maternal immune activation on embryonic brain development |
| title_full_unstemmed | The impact of maternal immune activation on embryonic brain development |
| title_short | The impact of maternal immune activation on embryonic brain development |
| title_sort | impact of maternal immune activation on embryonic brain development |
| topic | maternal immune activation neurogenesis neurodevelopment proliferation schizophrenia autism spectrum disorder |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2023.1146710/full |
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