Prefrontal Cortex Response to Prenatal Insult and Postnatal Opioid Exposure

Abstract

The influence of proinflammatory challenges, such as maternal immune activation (MIA) or postnatal exposure to drugs of abuse, on brain molecular pathways has been reported. On the other hand, the simultaneous effects of MIA and drugs of abuse have been less studied and sometimes offered inconsistent results. The effects of morphine exposure on a pig model of viral-elicited MIA were characterized in the prefrontal cortex of males and females using RNA-sequencing and gene network analysis. Interacting and main effects of morphine, MIA, and sex were detected in approximately 2000 genes (false discovery rate-adjusted p-value < 0.05). Among the enriched molecular categories (false discovery rate-adjusted p-value < 0.05 and −1.5 > normalized enrichment score > 1.5) were the cell adhesion molecule pathways associated with inflammation and neuronal development and the long-term depression pathway associated with synaptic strength. Gene networks that integrate gene connectivity and expression profiles displayed the impact of morphine-by-MIA interaction effects on the pathways. The cell adhesion molecules and long-term depression networks presented an antagonistic effect between morphine and MIA. The differential expression between the double-challenged group and the baseline saline-treated Controls was less extreme than the individual challenges. The previous findings advance the knowledge about the effects of prenatal MIA and postnatal morphine exposure on the prefrontal cortex pathways.

Genes Participating in the Ensheathment of Neurons Are Affected by Postnatal Stress and Maternal Immune Activation in the Pituitary Gland

“…The gene expression profiles suggest an antagonistic interaction between the stressors, opposite to that observed in the reproductive system's processes. The profiles observed in the present study were consistent with the over-expression of prefrontal cortex genes in the chemokine signaling pathway of the pigs exposed to MIA [49], and the under-expression of the genes annotated to the inflammation-associated pathways in the amygdala and hippocampus of the weaned pigs [16,46]. The importance of changes in the immune system pathway of the pituitary gland, in response to prenatal and weaning challenges, can also be related to the established immuno-enhancing role of many hormones secreted by the pituitary gland (e.g., prolactin, growth hormone, insulin growth factor-1, and thyroid hormones) in susceptibility to stressinduced disease [50].…”

Transcriptional characterization of cocaine withdrawal versus extinction within nucleus accumbens

“…7D), with several GO terms represented (e.g, phospholipid processes, histone acetylation, and calcium signaling) (Table 1). Indeed, several of these genes (e.g, SMAD3 , HTR7 , PPP1R17 ) 56–60 and their upstream regulators (e.g., STAT3, AR, mir-124) have previously been associated with cocaine exposure 61–64 (Fig. 7E).…”

Advances of Brain Transcriptomics

“…This Special Issue presents the results of another experiment by the same group of authors, which aimed to study the impact of proinflammatory challenges caused by maternal immune activation (MIA) and postnatal exposure to drugs of abuse (morphine) on the prefrontal cortex molecular pathways [ 8 ]. The range of interacting effects on the prefrontal cortex pathways were uncovered, providing new insights into the interplay between the effects of MIA and morphine.…”