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

Abstract

Immune challenges during gestation are associated with neurodevelopmental disorders and can interact with stress later in life. The pituitary gland participates in endocrine- and immune-related processes that influence development, growth, and reproduction and can modulate physiological and behavioral responses to challenges. The objective of this study was to investigate the effect of stressors at different time points on the molecular mechanisms of the pituitary gland and detect sex differences. RNA sequencing was used to profile the pituitary glands of female and male pigs exposed to weaning stress and virally induced maternal immune activation (MIA), relative to unchallenged groups. Significant effects (FDR-adjusted p-value < 0.05) of MIA and weaning stress were detected in 1829 and 1014 genes, respectively. Of these, 1090 genes presented significant interactions between stressors and sex. The gene ontology biological process of the ensheathment of neurons (GO:0007272), substance abuse, and immuno-related pathways, including the measles disease (ssc05162), encompasses many genes with profiles impacted by MIA and weaning stress. A gene network analysis highlighted the under-expression of myelin protein zero (Mpz) and inhibitors of DNA binding 4 (Id4) among the non-stressed males exposed to MIA, relative to the control and non-MIA males exposed to weaning stress, relative to non-stressed pigs. The detection of changes in the molecular mechanisms of the pituitary gland could advance our understanding of disruptions in the formation of the myelin sheath and the transmission of neuron-to-neuron signals in behavioral disorders associated with maternal immune activation and stress.

Immune and metabolic challenges induce changes in pain sensation and related pathways in the hypothalamus

“…4 ). In agreement with the previous network pattern, Oxt was overexpressed in the pituitary gland of 3-wk-old pigs exposed to gestational immune activation and weaning stress ( 44 ). Likewise, OXT agonists are effective modulators of virally induced inflammatory signals ( 14 ).…”

“…Corticosterone is a mediator of stress response and neuronal treatment, with this hormone increasing mitochondrial oxidation potential and offering neuroprotection against stress ( 89 ). The enrichment of the oxidative phosphorylation and ribosome categories was also observed in the amygdala, hippocampus, and pituitary gland of 3-wk-old pigs exposed to gestational immune activation and weaning stress ( 4 , 21 , 44 ). The correlated expression profile of the genes in the oxidative phosphorylation and ribosome pathways observed in the present study is supported by findings that neurodevelopmental pathologies associated with gestational immune activation, such as autism spectrum disorder, present aberrant ribosomal protein gene expression in the brain, at the same time as abnormal energy-related oxidative phosphorylation, respiratory, and electron transport chain functionality ( 90 ).…”

“…The enrichment of neuropeptide signaling was characterized by underexpression in pigs exposed to gestational immune activation and overexpression in metabolic-stressed males ( Table 1 ). The previous neuropeptide gene profiles were also detected in the pituitary gland of 3-wk-old pigs, including overexpression in males exposed to weaning stress that can be accompanied by temporary lower feed consumption and underexpression in pigs exposed to gestational immune activation ( 44 ). Similarly, changes in neuropeptide gene expression observed in the hypothalamus of rats exposed to metabolic stress have been associated with neural regulatory, behavioral, and physiological adaptations ( 45 ).…”

Editorial for the Molecular Mechanisms in Neurodevelopmental Disorders Special Issue

“…In particular, the possible contribution of prenatal programming through placental effects as an underlying mechanism that links to neurodevelopmental disorders risk, susceptible to environmental stressors (Hall et al, 2023;Woods et al, 2023) [9,10]. In fact, maternal immune activation is associated with changes in gene expression in the brain [11]. Understanding of alterations in myelin sheath formation and neuron-to-neuron signal transmission in behavioral disorders associated with maternal immune activation could be improved by detecting changes in the molecular structure of the gland.…”