Related Experiment Video
Updated: Jul 11, 2025
Author Spotlight: Understanding Adolescent Social Adversity Effects on Neurodevelopment in Mice
Published on: March 15, 2024
Prenatal infection and adolescent social adversity affect microglia, synaptic density, and behavior in male rats
Cyprien G J Guerrin1, Kavya Prasad1, Daniel A Vazquez-Matias1
1Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713, GZ, Groningen, the Netherlands.
Insights
Prenatal infection and adolescent social adversity impact neurodevelopment. Combined, they cause lasting glial changes and altered synaptic density, potentially influencing adult behavior and mental health.
Area of Science:
- Neuroscience
- Developmental Psychology
- Immunology
Background:
- Maternal infection and childhood trauma are linked to neurodevelopmental disorders like schizophrenia and depression.
- These disorders involve microglial cell changes, affecting synaptic pruning and leading to synaptic deficits.
Purpose of the Study:
- To investigate the combined and individual effects of prenatal infection and adolescent social adversity on behavior, microglia, and synaptic density.
- To understand the underlying mechanisms of neurodevelopmental and affective disorders.
Main Methods:
- Utilized a rat model with prenatal infection (poly I:C injection) and adolescent social defeat stress.
- Employed longitudinal in vivo imaging ( [11C]PBR28 PET) to assess glial reactivity (TSPO density).
- Analyzed microglial cell density, cytokine levels (IL-1β, IL-10), and synaptic density (synaptophysin) in adulthood.
Main Results:
- Prenatal infection alone or with social adversity induced hyperlocomotion in adulthood.
- Combined exposure caused a long-lasting increase in glial reactivity (TSPO) and microglial density in the frontal cortex.
- Prenatal infection increased IL-1β, while social adversity decreased IL-10; this IL-10 reduction was prevented by prenatal infection.
Conclusions:
- Prenatal infection and adolescent social adversity, especially in combination, induce lasting changes in glial cells and cytokine profiles.
- These changes may lead to altered synaptic pruning, increased synaptic density, and subsequent behavioral modifications in adulthood.
- Findings suggest a potential link between early-life stress, immune activation, and the pathophysiology of neurodevelopmental and affective disorders.
Abstract:
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.
