Terpenoid Backbone Biosynthesis Among Pig Hippocampal Pathways Impacted by Stressors

Overview

Journal Genes (Basel)

Publisher MDPI

Date 2022 May 28

PMID 35627199

Authors

Haley E Rymut

Laurie A Rund

Bruce R Southey

Rodney W Johnson

Sandra L Rodriguez-Zas

Affiliations

Soon will be listed here.

Abstract

Neurogenomic changes induced by maternal immune activation (MIA) during gestation and the social stress of weaning can alter brain plasticity in the hippocampus of offspring. The present study furthers the understanding of how these stressors impact hippocampus gene networks. The hippocampus transcriptome was profiled in pigs that were either exposed to MIA or not and were weaned or nursed. Overall, 1576 genes were differentially expressed (FDR-adjusted p-value < 0.05 and |log2 (fold change between pig groups)| > 1.2) in response to the main and interacting effects of MIA, weaning, and sex. Functional analysis identified 17 enriched immunological and neurological pathways in the Kyoto Encyclopedia of Genes and Genomes database. The enrichment of the terpenoid backbone biosynthesis pathway was characterized by genes under-expressed in MIA relative to non-MIA exposed, males relative to females, and weaned relative to nursed pigs. On the other hand, the enrichment of drug addiction pathways was characterized by gene over-expression in MIA relative to non-exposed pigs. Our results indicate that weaning and sex can modify the effects of MIA on the offspring hippocampus. This knowledge can aid in precise identification of molecular targets to reduce the prolonged effects of pre- and postnatal stressors.

Citing Articles

Xiaohua Funing decoction ameliorates non-alcoholic fatty liver disease by modulating the gut microbiota and bile acids.

Li Y, Zhao J Front Microbiol. 2025; 16:1511885.

PMID: 40012777 PMC: 11863611. DOI: 10.3389/fmicb.2025.1511885.

Incidence of alternative splicing associated with sex and opioid effects in the axon guidance pathway.

Southey B, Sunderland G, Gomez A, Bhamidi S, Rodriguez-Zas S Gene. 2025; 942:149215.

PMID: 39756548 PMC: 11863264. DOI: 10.1016/j.gene.2025.149215.

Epigenetic disruptions in the offspring hypothalamus in response to maternal infection.

Alsegehy S, Southey B, Hernandez A, Rund L, Antonson A, Nowak R Gene. 2024; 910:148329.

PMID: 38431234 PMC: 11826927. DOI: 10.1016/j.gene.2024.148329.

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

Rodriguez-Zas S, Nowak R, Antonson A, Rund L, Bhamidi S, Gomez A Physiol Genomics. 2024; 56(4):343-359.

PMID: 38189117 PMC: 11283907. DOI: 10.1152/physiolgenomics.00134.2023.

Prenatal and postnatal challenges affect the hypothalamic molecular pathways that regulate hormonal levels.

Rodriguez-Zas S, Southey N, Rund L, Antonson A, Nowak R, Johnson R PLoS One. 2023; 18(10):e0292952.

PMID: 37851674 PMC: 10584192. DOI: 10.1371/journal.pone.0292952.

References

Poletto R, Steibel J, Siegford J, Zanella A . Effects of early weaning and social isolation on the expression of glucocorticoid and mineralocorticoid receptor and 11beta-hydroxysteroid dehydrogenase 1 and 2 mRNAs in the frontal cortex and hippocampus of piglets. Brain Res. 2005; 1067(1):36-42. DOI: 10.1016/j.brainres.2005.10.001. View

Tyzio R, Nardou R, Ferrari D, Tsintsadze T, Shahrokhi A, Eftekhari S . Oxytocin-mediated GABA inhibition during delivery attenuates autism pathogenesis in rodent offspring. Science. 2014; 343(6171):675-9. DOI: 10.1126/science.1247190. View

Nazarian A, Sun W, Zhou L, Kemen L, Jenab S, Quinones-Jenab V . Sex differences in basal and cocaine-induced alterations in PKA and CREB proteins in the nucleus accumbens. Psychopharmacology (Berl). 2008; 203(3):641-50. DOI: 10.1007/s00213-008-1411-5. View

Szklarczyk D, Gable A, Nastou K, Lyon D, Kirsch R, Pyysalo S . The STRING database in 2021: customizable protein-protein networks, and functional characterization of user-uploaded gene/measurement sets. Nucleic Acids Res. 2020; 49(D1):D605-D612. PMC: 7779004. DOI: 10.1093/nar/gkaa1074. View

Mattei D, Ivanov A, Ferrai C, Jordan P, Guneykaya D, Buonfiglioli A . Maternal immune activation results in complex microglial transcriptome signature in the adult offspring that is reversed by minocycline treatment. Transl Psychiatry. 2017; 7(5):e1120. PMC: 5534948. DOI: 10.1038/tp.2017.80. View

Rymut H, Rund L, Bolt C, Villamil M, Southey B, Johnson R . The Combined Effect of Weaning Stress and Immune Activation during Pig Gestation on Serum Cytokine and Analyte Concentrations. Animals (Basel). 2021; 11(8). PMC: 8388404. DOI: 10.3390/ani11082274. View

Borcoi A, Patti C, Zanin K, Hollais A, Santos-Baldaia R, Ceccon L . Effects of prenatal immune activation on amphetamine-induced addictive behaviors: Contributions from animal models. Prog Neuropsychopharmacol Biol Psychiatry. 2015; 63:63-9. DOI: 10.1016/j.pnpbp.2015.05.015. View

Walker A, Nakamura T, Byrne R, Naicker S, Tynan R, Hunter M . Neonatal lipopolysaccharide and adult stress exposure predisposes rats to anxiety-like behaviour and blunted corticosterone responses: implications for the double-hit hypothesis. Psychoneuroendocrinology. 2009; 34(10):1515-25. DOI: 10.1016/j.psyneuen.2009.05.010. View

Wang X, Hagberg H, Nie C, Zhu C, Ikeda T, Mallard C . Dual role of intrauterine immune challenge on neonatal and adult brain vulnerability to hypoxia-ischemia. J Neuropathol Exp Neurol. 2007; 66(6):552-61. DOI: 10.1097/01.jnen.0000263870.91811.6f. View

10.

Giovanoli S, Engler H, Engler A, Richetto J, Voget M, Willi R . Stress in puberty unmasks latent neuropathological consequences of prenatal immune activation in mice. Science. 2013; 339(6123):1095-9. DOI: 10.1126/science.1228261. View

11.

Campbell J, Crenshaw J, Polo J . The biological stress of early weaned piglets. J Anim Sci Biotechnol. 2013; 4(1):19. PMC: 3651348. DOI: 10.1186/2049-1891-4-19. View

12.

Ghasemi Firouzabadi S, Kariminejad R, Vameghi R, Darvish H, Ghaedi H, Banihashemi S . Copy Number Variants in Patients with Autism and Additional Clinical Features: Report of VIPR2 Duplication and a Novel Microduplication Syndrome. Mol Neurobiol. 2016; 54(9):7019-7027. DOI: 10.1007/s12035-016-0202-y. View

13.

Rymut H, Rund L, Bolt C, Villamil M, Bender D, Southey B . Biochemistry and Immune Biomarkers Indicate Interacting Effects of Pre- and Postnatal Stressors in Pigs across Sexes. Animals (Basel). 2021; 11(4). PMC: 8067328. DOI: 10.3390/ani11040987. View

14.

Rymut H, Bolt C, Caputo M, Houser A, Antonson A, Zimmerman J . Long-Lasting Impact of Maternal Immune Activation and Interaction With a Second Immune Challenge on Pig Behavior. Front Vet Sci. 2020; 7:561151. PMC: 7732429. DOI: 10.3389/fvets.2020.561151. View

15.

Fernandez A, Dumon C, Guimond D, Tyzio R, Bonifazi P, Lozovaya N . The GABA Developmental Shift Is Abolished by Maternal Immune Activation Already at Birth. Cereb Cortex. 2018; 29(9):3982-3992. DOI: 10.1093/cercor/bhy279. View

16.

Mueller F, Scarborough J, Schalbetter S, Richetto J, Kim E, Couch A . Behavioral, neuroanatomical, and molecular correlates of resilience and susceptibility to maternal immune activation. Mol Psychiatry. 2020; 26(2):396-410. PMC: 7850974. DOI: 10.1038/s41380-020-00952-8. View

17.

Zech M, Kopajtich R, Steinbrucker K, Bris C, Gueguen N, Feichtinger R . Variants in Mitochondrial ATP Synthase Cause Variable Neurologic Phenotypes. Ann Neurol. 2021; 91(2):225-237. PMC: 9939050. DOI: 10.1002/ana.26293. View

18.

Deb S, Phukan B, Dutta A, Paul R, Bhattacharya P, Manivasagam T . Natural Products and Their Therapeutic Effect on Autism Spectrum Disorder. Adv Neurobiol. 2020; 24:601-614. DOI: 10.1007/978-3-030-30402-7_22. View

19.

Capellan R, Orihuel J, Marcos A, Ucha M, Moreno-Fernandez M, Casquero-Veiga M . Interaction between maternal immune activation and peripubertal stress in rats: impact on cocaine addiction-like behaviour, morphofunctional brain parameters and striatal transcriptome. Transl Psychiatry. 2023; 13(1):84. PMC: 9995324. DOI: 10.1038/s41398-023-02378-6. View

20.

Singh Anand K, Dhikav V . Hippocampus in health and disease: An overview. Ann Indian Acad Neurol. 2013; 15(4):239-46. PMC: 3548359. DOI: 10.4103/0972-2327.104323. View