Prenatal infection and adolescent social adversity affect microglia, synaptic density, and behavior in male rats

1. Neurobiol Stress. 2023 Oct 19;27:100580. doi: 10.1016/j.ynstr.2023.100580.
eCollection 2023 Nov.

Prenatal infection and adolescent social adversity affect microglia, synaptic
density, and behavior in male rats.

Guerrin CGJ(1), Prasad K(1), Vazquez-Matias DA(1), Zheng J(1),
Franquesa-Mullerat M(1), Barazzuol L(2)(3), Doorduin J(1), de Vries EFJ(1).

Author information:
(1)Department of Nuclear Medicine and Molecular Imaging, University Medical
Center Groningen, University of Groningen, Hanzeplein 1, 9713, GZ, Groningen,
the Netherlands.
(2)Department of Radiation Oncology, University of Groningen, University Medical
Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, the Netherlands.
(3)Department of Biomedical Sciences of Cells and Systems, University of
Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ,
Groningen, the Netherlands.

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.

© 2023 Published by Elsevier Inc.

DOI: 10.1016/j.ynstr.2023.100580
PMCID: PMC10618826
PMID: 37920548

Conflict of interest statement: The authors declare that they have no known
competing financial interests or personal relationships that could have appeared
to influence the work reported in this paper.

Auteurs Bordeaux Neurocampus