Alterations in Retrotransposition, Synaptic Connectivity, and Myelination Implicated by Transcriptomic Changes Following Maternal Immune Activation in Nonhuman Primates

Abstract

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

Disruption of Alternative Splicing in the Amygdala of Pigs Exposed to Maternal Immune Activation

“…MAG was under-expressed in the prefrontal cortex of MIA rats exposed to Poly(I:C) during development [44], in the prefrontal cortex and nucleus accumbens of MIA mice exposed to Poly(I:C) during development [45], and in the cerebellum of mice exposed to influenza-elicited MIA [46]. On the other hand, the over-expression of a MAG isoform in MIA pigs (albeit less extreme than the previously discussed under-expressed isoform) is in agreement with the over-expression of MAG in the hippocampus of MIA offspring of Poly(I:C)-challenged rhesus macaques [47]. Our findings provide a possible explanation of the apparent contradiction in the MAG profiles associated with MIA.…”

Mouse models of immune dysfunction: their neuroanatomical differences reflect their anxiety-behavioural phenotype

“…The corpus callosum, thalamus, striatum, and midbrain were amongst the most-affected structures across all mouse models, which reflects neurological findings in autoimmune disorders [ 69 – 72 ]. Furthermore, several genes associated with myelination are expressed in these regions, which is consistent with molecular studies conducted on MIA model primates [ 73 ]. Preferentially expressed genes were also homologous to human genes associated with MS.…”

Primate Models as a Translational Tool for Understanding Prenatal Origins of Neurodevelopmental Disorders Associated With Maternal Infection

“…4.3.2 1 st versus 2 nd Trimester Exposure Cohort. We then conducted a pilot comparison of NHP offspring born to dams that received three Poly ICLC injections in the late 1 st (N=6) or 2 nd (N=7) trimesters that included an evaluation of offspring behavior ( 140 , 141 ), immune ( 142 ), and brain ( 143 , 144 , 145 ) development. Although there were no consistent differences early in development, the MIA offspring exposed to MIA in either trimester displayed increased repetitive behaviors and changes in social development as they matured, with more differences specifically between first and second trimester offspring with control ones summarized in Table 2 ( 140 ).…”

“…The MIA-treated animals also exhibited alterations in immune function relevant to NDDs, characterized by elevated production of innate inflammatory cytokines both at baseline and following stimulation at one year of age, and at four years of age, elevated IL-1b paired with increased production of T-cell helper type (TH)-2 cytokines, IL-4, and IL-13 ( 142 ). Finally, RNA sequencing of prefrontal cortex, anterior cingulate, hippocampus, and primary visual cortex implicated alterations in transposable element biology, synaptic connectivity, and myelination with relative hippocampal vulnerability in the adolescent brain of MIA-exposed NHPs ( 144 ). We have also recently replicated the findings of aberrant dendritic morphology in the DLPFC ( 139 ), with both first and second trimester MIA-exposed monkeys exhibiting an increase in dendritic branching in pyramidal cells in both infra- and supragranular layers in DLPFC, paired with a significant decrease in apical dendrite diameter in the infragranular layers of the DLPFC.…”