Abstract
Background
Maternal immune activation (MIA) is a proposed risk factor for multiple neuropsychiatric
disorders, including schizophrenia. However, the molecular mechanisms through which
MIA imparts risk remain poorly understood. A recently developed nonhuman primate model
of exposure to the viral mimic poly:ICLC during pregnancy shows abnormal social and
repetitive behaviors and elevated striatal dopamine, a molecular hallmark of human
psychosis, providing an unprecedented opportunity for studying underlying molecular
correlates.
Methods
We performed RNA sequencing across psychiatrically relevant brain regions (prefrontal
cortex, anterior cingulate, hippocampus) and primary visual cortex for comparison
from 3.5- to 4-year-old male MIA-exposed and control offspring—an age comparable to
mid adolescence in humans.
Results
We identify 266 unique genes differentially expressed in at least one brain region,
with the greatest number observed in hippocampus. Co-expression networks identified
region-specific alterations in synaptic signaling and oligodendrocytes. Although we
observed temporal and regional differences, transcriptomic changes were shared across
first- and second-trimester exposures, including for the top differentially expressed
genes—PIWIL2 and MGARP. In addition to PIWIL2, several other regulators of retrotransposition and endogenous transposable elements
were dysregulated following MIA, potentially connecting MIA to retrotransposition.
Conclusions
Together, these results begin to elucidate the brain-level molecular processes through
which MIA may impart risk for psychiatric disease.
Keywords
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Article info
Publication history
Published online: November 02, 2020
Accepted:
October 9,
2020
Received in revised form:
October 7,
2020
Received:
February 20,
2020
Identification
Copyright
© 2020 Society of Biological Psychiatry.
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- Maternal Immune Activation and Retrotransposition in Neurodevelopmental DisordersBiological PsychiatryVol. 89Issue 9
- PreviewEpidemiologic studies have repeatedly implicated infectious and noninfectious maternal immune activation (MIA) in the etiology of neuropsychiatric illnesses (1). MIA can trigger several pathophysiological processes, including inflammation and oxidative stress in maternal and fetal compartments, activation of maternal stress response systems, and temporary micronutrient and/or macronutrient deficiencies, as well as disruption of placental functions (2). When occurring during sensitive periods of fetal development, these pathophysiological processes have the potential to change the offspring’s neurodevelopmental trajectories and increase their risk to develop neuropsychiatric disorders later in life (2).
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