Effects of maternal immune activation in porcine transcript isoforms of neuropeptide and receptor genes

Southey, Bruce R.; Zhang, Pan; Keever, Marissa R; Rymut, Haley E; Johnson, Rodney W.; Sweedler, Jonathan V.; Rodriguez-Zas, Sandra L.

doi:10.31083/j.jin.2021.01.332

Cited by 11 publications

(10 citation statements)

References 107 publications

(128 reference statements)

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“…The effects of MIA on the amygdala may influence the offspring's neuroendocrine profiles, social and sexually dimorphic behaviors, cognition, and the response to stressors [22,23]. Using a pig model of MIA elicited by a live virus, we reported that three-weekold pigs presented changes in the expression pattern of genes annotated to neurodevel-Immuno 2021, 1 500 opmental disorders, ASD, and SSD in the amygdala [24,25]. Subsequent investigations of the impact of the first challenge by MIA followed by weaning stress at three weeks of age confirmed the higher blood cortisol levels in weaned pigs relative to nursed pigs [7] and uncovered the potential modulating impact of MIA on the effects of weaning on genes annotated to autoimmune diseases and cell adhesion molecules [3].…”

Section: Introductionmentioning

confidence: 97%

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

Southey

Keever-Keigher

Rymut

et al. 2021

Immuno

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The inflammatory response of gestating females to infection or stress can disrupt gene expression in the offspring’s amygdala, resulting in lasting neurodevelopmental, physiological, and behavioral disorders. The effects of maternal immune activation (MIA) can be impacted by the offspring’s sex and exposure to additional stressors later in life. The objectives of this study were to investigate the disruption of alternative splicing patterns associated with MIA in the offspring’s amygdala and characterize this disruption in the context of the second stress of weaning and sex. Differential alternative splicing was tested on the RNA-seq profiles of a pig model of viral-induced MIA. Compared to controls, MIA was associated with the differential alternative splicing (FDR-adjusted p-value < 0.1) of 292 and 240 genes in weaned females and males, respectively, whereas 132 and 176 genes were differentially spliced in control nursed female and male, respectively. The majority of the differentially spliced (FDR-adjusted p-value < 0.001) genes (e.g., SHANK1, ZNF672, KCNA6) and many associated enriched pathways (e.g., Fc gamma R-mediated phagocytosis, non-alcoholic fatty liver disease, and cGMP-PKG signaling) have been reported in MIA-related disorders including autism and schizophrenia in humans. Differential alternative splicing associated with MIA was detected in the gene MAG across all sex-stress groups except for unstressed males and SLC2A11 across all groups except unstressed females. Precise understanding of the effect of MIA across second stressors and sexes necessitates the consideration of splicing isoform profiles.

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Section: Introductionmentioning

confidence: 97%

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

Southey

Keever-Keigher

Rymut

et al. 2021

Immuno

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“…Tylopoda and Cetacean species presented IAPP sequences encompassing discrepancies consistent with pseudogenes including stop codons and lack of a signal peptide. Chacoan peccary ( Catagonus wagneri ) and all the camelid species studied, along with previous reports on the pig IAPP [ 18 ], lack the sequence corresponding to traditional cleavage sites, although analysis of RNA-seq data indicated that IAPP is expressed in pigs [ 49 ].…”

Section: Discussionmentioning

confidence: 94%

Changes in Neuropeptide Prohormone Genes among Cetartiodactyla Livestock and Wild Species Associated with Evolution and Domestication

Southey

Rodríguez-Zas

2022

Veterinary Sciences

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The impact of evolution and domestication processes on the sequences of neuropeptide prohormone genes that participate in cell–cell signaling influences multiple biological process that involve neuropeptide signaling. This information is important to understand the physiological differences between Cetartiodactyla domesticated species such as cow, pig, and llama and wild species such as hippopotamus, giraffes, and whales. Systematic analysis of changes associated with evolutionary and domestication forces in neuropeptide prohormone protein sequences that are processed into neuropeptides was undertaken. The genomes from 118 Cetartiodactyla genomes representing 22 families were mined for 98 neuropeptide prohormone genes. Compared to other Cetartiodactyla suborders, Ruminantia preserved PYY2 and lost RLN1. Changes in GNRH2, IAPP, INSL6, POMC, PRLH, and TAC4 protein sequences could result in the loss of some bioactive neuropeptides in some families. An evolutionary model suggested that most neuropeptide prohormone genes disfavor sequence changes that incorporate large and hydrophobic amino acids. A compelling finding was that differences between domestic and wild species are associated with the molecular system underlying ‘fight or flight’ responses. Overall, the results demonstrate the importance of simultaneously comparing the neuropeptide prohormone gene complement from close and distant-related species. These findings broaden the foundation for empirical studies about the function of the neuropeptidome associated with health, behavior, and food production.

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“…CD40/CD154, as costimulatory molecules, play a key regulatory role in the immune response (Díaz et al, 2021). The immune system plays roles in supervising, regulating, and responding to external factors in a stressful manner, and also in causing optic nerve damage (Southey et al, 2021). Research studies have shown that CD4+ T cells exhibit strong stimulatory responses in GC, such as enhanced proliferation and increased secretion of pro‐inflammatory cytokines (Yang et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

“…This suggests that some causative factors other than IOP are involved in GC progression. Research studies have revealed the presence of significant autoimmune reactions in patients with different types of GC (Geyer & Levo, 2020; Southey et al, 2021; Wang & Wei, 2021). Therefore, further exploration of key immune‐related molecules might provide potential targets for immunomodulatory therapy of OHG.CD40/CD154 (CD40L), as a costimulatory signal for T cell activation, plays a key role in several aspects of the immune response (Díaz et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Insights into CD154‐mediated pathways in ocular hypertensive glaucoma: The role of Müller cells and P2X7 in retinal neuroprotection and therapeutic potential

Liu

Nie

et al. 2023

Cell Biology International

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An elevation of pathologic intraocular pressure (IOP) is the greatest risk factor for glaucoma. CD154 has been reported to bind to CD40 expressed by orbital fibroblasts and be involved in immune and inflammatory responses. However, the function and mechanism of CD154 in ocular hypertensive glaucoma (OHG) are not fully understood. We isolated and characterized Müller cells and subsequently examined the effect of CD154 on ATP release from those cells. After being cocultured with CD154-pretreated Müller cells, retinal ganglion cells (RGCs) were treated with P2X7 siRNAs or a P2X7 inhibitor. Furthermore, mouse models of glaucoma (GC) were injected with P2X7 shRNA. p21, p53, and P2X7 expression were examined, and cellular senescence and apoptosis were detected by β-Gal and TUNEL staining, retinal pathology was examined by H&E staining, and CD154 and β-Gal expression were detected by ELISA. CD154 induced ATP release from Müller cells and accelerated the senescence and apoptosis of RGCs that had been cocultured with Müller cells. We also found that treatment with P2X7 could attenuate the senescence and apoptosis of RGCs mediated by Müller cells pretreated with CD154. In vivo studies in GC model mice verified that P2X7 silencing attenuated pathological damage and prevented the senescence and apoptosis of retinal tissue. The study demonstrates how CD154 accelerates the aging and apoptosis of RGCs by co-cultivating Müller cells pretreated with CD154 in OHG. The research implies that CD154 has the potential to become a new therapeutic target for ocular hypertension glaucoma, providing a new research direction for its treatment.

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Effects of maternal immune activation in porcine transcript isoforms of neuropeptide and receptor genes

Cited by 11 publications

References 107 publications

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

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

Changes in Neuropeptide Prohormone Genes among Cetartiodactyla Livestock and Wild Species Associated with Evolution and Domestication

Insights into CD154‐mediated pathways in ocular hypertensive glaucoma: The role of Müller cells and P2X7 in retinal neuroprotection and therapeutic potential

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