Biology subjects

Schumann, C. M.

Publications and source records attributed to Schumann, C. M..

2 recordsLinked to original sources

bioRxiv2020

Maternal immune activation during pregnancy alters early neurobehavioral development in nonhuman primate offspring

BackgroundHuman epidemiologic studies have implicated exposure to infectious or inflammatory insults during gestation in the etiology of neurodevelopmental disorders. Rodent models of maternal immune activation (MIA) have identified the maternal immune response as the critical link between maternal infection and aberrant brain and behavior development in offspring. The nonhuman primate MIA model provides an opportunity to maximize the translational utility of this model in a species more closely related to humans. MethodsHere we evaluate the effects of MIA on brain and behavioral development in the rhesus monkey (Macaca mulatta). A modified form of the viral mimic, Polyinosinic-polycytidylic acid (PolyIC), was delivered to pregnant rhesus monkeys (n=14) in the late first trimester to stimulate a maternal immune response. Control dams received saline injections at the same gestational time points (n=10) or were untreated (n=4). ResultsMIA-treated dams exhibited a strong immune response as indexed by transient increases in sickness behavior, temperature and inflammatory cytokines. MIA-exposed offspring developed species typical milestones and demonstrate subtle changes in early in social development. However, magnetic resonance imaging demonstrated significant gray matter volume reductions in prefrontal and frontal cortices at 6, 12 and 24 months of age. ConclusionsThese findings provide new insights into the emergence of neuropathology in MIA-exposed primates and have implications for the pathophysiology of human psychiatric disorders associated with maternal gestational infection.

neuroscience↗

bioRxiv2020

Alterations in retrotransposition, synaptic connectivity, and myelination implicated by transcriptomic changes following maternal immune activation in non-human primates

BackgroundMaternal immune activation (MIA) is a proposed risk factor for multiple neurodevelopmental and psychiatric disorders, including schizophrenia. However, the molecular and neurobiological mechanisms through which MIA imparts risk for these disorders 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 mechanistic dissection. MethodsWe performed RNA-sequencing across four psychiatrically-relevant brain regions (prefrontal cortex, anterior cingulate, hippocampus, and primary visual cortex) from 3.5-4-year old male MIA-exposed and control offspring--an age comparable to mid adolescence in humans. ResultsWe identify 266 unique genes differentially expressed (DE) 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. Across regions, we observed temporal and regional differences, but transcriptomic changes were largely similar across 1st or 2nd trimester MIA exposures, including for the top DE genes--PIWIL2 and MGARP. In addition to PIWIL2, several other known regulators of retrotransposition, as well as endogenous transposable elements were dysregulated in MIA offspring. ConclusionsTogether, these results begin to elucidate the brain-level molecular mechanisms through which MIA may impart risk for psychiatric disease.

neuroscience↗