Dataset Information

Interacting impact of maternal inflammatory response and stress on the amygdala transcriptome of pigs.

ABSTRACT: Changes at the molecular level capacitate the plasticity displayed by the brain in response to stress stimuli. Weaning stress can trigger molecular changes that influence the physiology of the offspring. Likewise, maternal immune activation (MIA) during gestation has been associated with behavior disorders and molecular changes in the amygdala of the offspring. This study advances the understanding of the effects of pre-and postnatal stressors in amygdala gene networks. The amygdala transcriptome was profiled on female and male pigs that were either exposed to viral-elicited MIA or not and were weaned or nursed. Overall, 111 genes presented interacting or independent effects of weaning, MIA or sex (FDR-adjusted P-value < 0.05). PIGY upstream reading frame (PYURF) and orthodenticle homeobox 2 (OTX2) are genes associated with MIA-related neurological disorders, and presented significant under-expression in weaned relative to nursed pigs exposed to MIA, with an opposite pattern was observed in non-MIA pigs. Enriched among the genes presenting highly over- or under-expression profiles were 24 KEGG pathways including inflammation, and neurological disorders. Our results indicate that MIA and sex can modulate the effect of weaning stress on the molecular mechanisms in the developing brain. Our findings can help identify molecular targets to ameliorate the effects of pre-and postnatal stressors on behaviors regulated by the amygdala such as aggression and feeding.

SUBMITTER: Keever-Keigher MR

PROVIDER: S-EPMC8496236 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BACKGROUND:Adverse childhood experiences (ACEs), such as abuse or chronic stress, program an exaggerated adult inflammatory response to stress. Emerging rodent research suggests that the gut microbiome may be a key mediator in the association between early life stress and dysregulated glucocorticoid-immune response. However, ACE impact on inflammatory response to stress, or on the gut microbiome, have not been studied in human pregnancy, when inflammation increases risk of poor outcomes. The aim of this study was to assess the relationships among ACE, the gut microbiome, and cytokine response to stress in pregnant women. METHODS:Physically and psychiatrically healthy adult pregnant women completed the Adverse Childhood Experiences Questionnaire (ACE-Q) and gave a single stool sample between 20 and 26?weeks gestation. Stool DNA was isolated and 16S sequencing was performed. Three 24-hour food recalls were administered to assess dietary nutrient intake. A subset of women completed the Trier Social Stress Test (TSST) at 22-34?weeks gestation; plasma interleukin-6 (IL-6), interleukin-1? (IL-1?), high sensitivity C-reactive protein (hsCRP), tumor necrosis factor ? (TNF-?), and cortisol were measured at four timepoints pre and post stressor, and area under the curve (AUC) was calculated. RESULTS:Forty-eight women completed the ACE-Q and provided stool; 19 women completed the TSST. Women reporting 2 or more ACEs (high ACE) had greater differential abundance of gut Prevotella than low ACE participants (q?=?5.7?×?10^-13). Abundance of several gut taxa were significantly associated with cortisol, IL-6, TNF-? and CRP AUCs regardless of ACE status. IL-6 response to stress was buffered among high ACE women with high intake of docosahexaenoic acid (DHA) (p?=?0.03) and eicosapentaenoic acid (EPA) (p?=?0.05). DISCUSSION:Our findings suggest that multiple childhood adversities are associated with changes in gut microbiota composition during pregnancy, and such changes may contribute to altered inflammatory and glucocorticoid response to stress. While preliminary, this is the first study to demonstrate an association between gut microbiota and acute glucocorticoid-immune response to stress in a clinical sample. Finally, exploratory analyses suggested that high ACE women with high dietary intake of ?-3 polyunsaturated fatty acids (PUFAs) had a dampened inflammatory response to acute stress, suggesting potentially protective effects of ?-3s in this high-risk population. Given the adverse effects of inflammation on pregnancy and the developing fetus, mechanisms by which childhood adversity influence the gut-brain axis and potential protective factors such as diet should be further explored.

Dataset Information

Interacting impact of maternal inflammatory response and stress on the amygdala transcriptome of pigs.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets