Prenatal infection and adolescent social adversity affect microglia, synaptic density, and behavior in male rats
Maternal infection during pregnancy and childhood social trauma have been associated with neurodevelopmental and affective disorders, such as schizophrenia, autism spectrum disorders, bipolar disorder and depression. These disorders are characterized by changes in microglial cells, which play a nota...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-11-01
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| Series: | Neurobiology of Stress |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352289523000681 |
| _version_ | 1797405399888953344 |
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| author | Cyprien G.J. Guerrin Kavya Prasad Daniel A. Vazquez-Matias Jing Zheng Maria Franquesa-Mullerat Lara Barazzuol Janine Doorduin Erik F.J. de Vries |
| author_facet | Cyprien G.J. Guerrin Kavya Prasad Daniel A. Vazquez-Matias Jing Zheng Maria Franquesa-Mullerat Lara Barazzuol Janine Doorduin Erik F.J. de Vries |
| author_sort | Cyprien G.J. Guerrin |
| collection | DOAJ |
| description | Maternal infection during pregnancy and childhood social trauma have been associated with neurodevelopmental and affective disorders, such as schizophrenia, autism spectrum disorders, bipolar disorder and depression. These disorders are characterized by changes in microglial cells, which play a notable role in synaptic pruning, and synaptic deficits. Here, we investigated the effect of prenatal infection and social adversity during adolescence – either alone or in combination – on behavior, microglia, and synaptic density. Male offspring of pregnant rats injected with poly I:C, mimicking prenatal infection, were exposed to repeated social defeat during adolescence. We found that maternal infection during pregnancy prevented the reduction in social behavior and increase in anxiety induced by social adversity during adolescence. Furthermore, maternal infection and social adversity, alone or in combination, induced hyperlocomotion in adulthood. Longitudinal in vivo imaging with [11C]PBR28 positron emission tomography revealed that prenatal infection alone and social adversity during adolescence alone induced a transient increase in translocator protein TSPO density, an indicator of glial reactivity, whereas their combination induced a long-lasting increase that remained until adulthood. Furthermore, only the combination of prenatal infection and social adversity during adolescence induced an increase in microglial cell density in the frontal cortex. Prenatal infection increased proinflammatory cytokine IL-1β protein levels in hippocampus and social adversity reduced anti-inflammatory cytokine IL-10 protein levels in hippocampus during adulthood. This reduction in IL-10 was prevented if rats were previously exposed to prenatal infection. Adult offspring exposed to prenatal infection or adolescent social adversity had a higher synaptic density in the frontal cortex, but not hippocampus, as evaluated by synaptophysin density. Interestingly, such an increase in synaptic density was not observed in rats exposed to the combination of prenatal infection and social adversity, perhaps due to the long-lasting increase in microglial density, which may lead to an increase in microglial synaptic pruning. These findings suggest that changes in microglia activity and cytokine release induced by prenatal infection and social adversity during adolescence may be related to a reduced synaptic pruning, resulting in a higher synaptic density and behavioral changes in adulthood. |
| first_indexed | 2024-03-09T03:09:53Z |
| format | Article |
| id | doaj.art-6013f148061e45d7aa8301774c80516a |
| institution | Directory Open Access Journal |
| issn | 2352-2895 |
| language | English |
| last_indexed | 2024-03-09T03:09:53Z |
| publishDate | 2023-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Stress |
| spelling | doaj.art-6013f148061e45d7aa8301774c80516a2023-12-04T05:23:00ZengElsevierNeurobiology of Stress2352-28952023-11-0127100580Prenatal infection and adolescent social adversity affect microglia, synaptic density, and behavior in male ratsCyprien G.J. Guerrin0Kavya Prasad1Daniel A. Vazquez-Matias2Jing Zheng3Maria Franquesa-Mullerat4Lara Barazzuol5Janine Doorduin6Erik F.J. de Vries7Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713, GZ, Groningen, the NetherlandsDepartment of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713, GZ, Groningen, the NetherlandsDepartment of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713, GZ, Groningen, the NetherlandsDepartment of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713, GZ, Groningen, the NetherlandsDepartment of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713, GZ, Groningen, the NetherlandsDepartment of Radiation Oncology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, the Netherlands; Department of Biomedical Sciences of Cells and Systems, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, the NetherlandsDepartment of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713, GZ, Groningen, the Netherlands; Corresponding author.Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713, GZ, Groningen, the NetherlandsMaternal infection during pregnancy and childhood social trauma have been associated with neurodevelopmental and affective disorders, such as schizophrenia, autism spectrum disorders, bipolar disorder and depression. These disorders are characterized by changes in microglial cells, which play a notable role in synaptic pruning, and synaptic deficits. Here, we investigated the effect of prenatal infection and social adversity during adolescence – either alone or in combination – on behavior, microglia, and synaptic density. Male offspring of pregnant rats injected with poly I:C, mimicking prenatal infection, were exposed to repeated social defeat during adolescence. We found that maternal infection during pregnancy prevented the reduction in social behavior and increase in anxiety induced by social adversity during adolescence. Furthermore, maternal infection and social adversity, alone or in combination, induced hyperlocomotion in adulthood. Longitudinal in vivo imaging with [11C]PBR28 positron emission tomography revealed that prenatal infection alone and social adversity during adolescence alone induced a transient increase in translocator protein TSPO density, an indicator of glial reactivity, whereas their combination induced a long-lasting increase that remained until adulthood. Furthermore, only the combination of prenatal infection and social adversity during adolescence induced an increase in microglial cell density in the frontal cortex. Prenatal infection increased proinflammatory cytokine IL-1β protein levels in hippocampus and social adversity reduced anti-inflammatory cytokine IL-10 protein levels in hippocampus during adulthood. This reduction in IL-10 was prevented if rats were previously exposed to prenatal infection. Adult offspring exposed to prenatal infection or adolescent social adversity had a higher synaptic density in the frontal cortex, but not hippocampus, as evaluated by synaptophysin density. Interestingly, such an increase in synaptic density was not observed in rats exposed to the combination of prenatal infection and social adversity, perhaps due to the long-lasting increase in microglial density, which may lead to an increase in microglial synaptic pruning. These findings suggest that changes in microglia activity and cytokine release induced by prenatal infection and social adversity during adolescence may be related to a reduced synaptic pruning, resulting in a higher synaptic density and behavioral changes in adulthood.http://www.sciencedirect.com/science/article/pii/S2352289523000681Maternal immune activationSocial adversityMicrogliaSynaptic densitySynaptophysinNeurodevelopmental disorders |
| spellingShingle | Cyprien G.J. Guerrin Kavya Prasad Daniel A. Vazquez-Matias Jing Zheng Maria Franquesa-Mullerat Lara Barazzuol Janine Doorduin Erik F.J. de Vries Prenatal infection and adolescent social adversity affect microglia, synaptic density, and behavior in male rats Neurobiology of Stress Maternal immune activation Social adversity Microglia Synaptic density Synaptophysin Neurodevelopmental disorders |
| title | Prenatal infection and adolescent social adversity affect microglia, synaptic density, and behavior in male rats |
| title_full | Prenatal infection and adolescent social adversity affect microglia, synaptic density, and behavior in male rats |
| title_fullStr | Prenatal infection and adolescent social adversity affect microglia, synaptic density, and behavior in male rats |
| title_full_unstemmed | Prenatal infection and adolescent social adversity affect microglia, synaptic density, and behavior in male rats |
| title_short | Prenatal infection and adolescent social adversity affect microglia, synaptic density, and behavior in male rats |
| title_sort | prenatal infection and adolescent social adversity affect microglia synaptic density and behavior in male rats |
| topic | Maternal immune activation Social adversity Microglia Synaptic density Synaptophysin Neurodevelopmental disorders |
| url | http://www.sciencedirect.com/science/article/pii/S2352289523000681 |
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