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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.

Prenatal stress often results in maternal immune activation (MIA) that can impact prenatal brain development, molecular processes, and substrates and products of metabolism that participate in physiological processes at later stages of life. Postnatal metabolic and immunological stressors can affect brain metabolites later in life, independently or in combination with prenatal stressors. The effects of prenatal and postnatal stressors on hippocampal metabolites were studied using a pig model of viral MIA exposed to immunological and metabolic stressors at 60 days of age using gas chromatography mass spectrometry. Postnatal stress and MIA elicited effects (FDR-adjusted p-value < 0.1) on fifty-nine metabolites, while eight metabolites exhibited an interaction effect. The hippocampal metabolites impacted by MIA or postnatal stress include 4-aminobutanoate (GABA), adenine, fumarate, glutamate, guanine, inosine, ornithine, putrescine, pyruvate, and xanthine. Metabolites affected by MIA or postnatal stress encompassed eight significantly (FDR-adjusted p-value < 0.1) enriched Kyoto Encyclopedia of Genes and Genomes Database (KEGG) pathways. The enriched arginine biosynthesis and glutathione metabolism pathways included metabolites that are also annotated for the urea cycle and polyamine biosynthesis pathways. Notably, the prenatal and postnatal challenges were associated with disruption of the glutathione metabolism pathway and changes in the levels of glutamic acid, glutamate, and purine nucleotide metabolites that resemble patterns elicited by drugs of abuse and may underlie neuroinflammatory processes. The combination of MIA and postnatal stressors also supported the double-hit hypothesis, where MIA amplifies the impact of stressors later in life, sensitizing the hippocampus of the offspring to future challenges. The metabolites and pathways characterized in this study offer evidence of the role of immunometabolism in understanding the impact of MIA and stressors later in life on memory, spatial navigation, neuropsychiatric disorders, and behavioral disorders influenced by the hippocampus.

Cover cropping (CC) is a promising in-field practice to mitigate soil health degradation and nitrogen (N) losses from excessive N fertilization. Soil N-cycling microbial communities are the fundamental drivers of these processes, but how they respond to CC under field conditions is poorly documented for typical agricultural systems. Our objective was to investigate this relationship for a long-term (36 years) corn [Zea mays L.] monocultures under three N fertilizer rates (N0, N202, and N269; kg N/ha), where a mixture of cereal rye [Secale cereale L.] and hairy vetch [Vicia villosa Roth.] was introduced for two consecutive years, using winter fallows as controls (BF). A 3 × 2 split-plot arrangement of N rates and CC treatments in a randomized complete block design with three replications was deployed. Soil chemical and physical properties and potential nitrification (PNR) and denitrification (PDR) rates were measured along with functional genes, including nifH, archaeal and bacterial amoA, nirK, nirS, and nosZ-I, sequenced in Illumina MiSeq system and quantified in high-throughput quantitative polymerase chain reaction (qPCR). The abundances of nifH, archaeal amoA, and nirS decreased with N fertilization (by 7.9, 4.8, and 38.9 times, respectively), and correlated positively with soil pH. Bacterial amoA increased by 2.4 times with CC within N269 and correlated positively with soil nitrate. CC increased the abundance of nirK by 1.5 times when fertilized. For both bacterial amoA and nirK, N202 and N269 did not differ from N0 within BF. Treatments had no significant effects on nosZ-I. The reported changes did not translate into differences in functionality as PNR and PDR did not respond to treatments. These results suggested that N fertilization disrupts the soil N-cycling communities of this system primarily through soil acidification and high nutrient availability. Two years of CC may not be enough to change the N-cycling communities that adapted to decades of disruption from N fertilization in corn monoculture. This is valuable primary information to understand the potentials and limitations of CC when introduced into long-term agricultural systems.

The prolonged effects of maternal immune activation in response stressors during gestation on the offspring’s molecular pathways after birth are beginning to be understood. An association between maternal immune activation and neurodevelopmental and behavior disorders such as autism and schizophrenia spectrum disorders has been detected in long-term gene dysregulation. The incidence of alternative splicing among neuropeptides and neuropeptide receptor genes, critical cell-cell signaling molecules, associated with behavior may compromise the replicability of reported maternal immune activation effects at the gene level. This study aims to advance the understanding of the effect of maternal immune activation on transcript isoforms of the neuropeptide system (including neuropeptide, receptor and connecting pathway genes) underlying behavior disorders later in life. Recognizing the wide range of bioactive peptides and functional receptors stemming from alternative splicing, we studied the effects of maternal immune activation at the transcript isoform level on the hippocampus and amygdala of three-week-old pigs exposed to maternal immune activation due to viral infection during gestation. In the hippocampus and amygdala, 29 and 9 transcript isoforms, respectively, had maternal immune activation effects (P-value < 0.01). We demonstrated that the study of the effect of maternal immune activation on neuropeptide systems at the isoform level is necessary to expose opposite effects among transcript isoforms from the same gene. Genes were maternal immune activation effects have also been associated with neurodevelopmental and behavior disorders. The characterization of maternal immune activation effects at the transcript isoform level advances the understanding of neurodevelopmental disorders and identifies precise therapeutic targets.

No studies, to date, have scrutinized the role of a priori dietary patterns on prognosis following a head and neck squamous cell carcinoma (HNSCC) diagnosis. The purpose of this analysis was to evaluate the associations between adherence to six a priori defined diet quality indices (including AHEI-2010, aMED, DASH, and three low-carbohydrate indices) throughout the first 3 years of observation and all-cause and cancer-specific mortalities in 468 newly diagnosed HNSCC patients from the University of Michigan Head and Neck Specialized Program of Research Excellence (UM-SPORE). The dietary intake data were measured using a food frequency questionnaire administered at three annual time points commencing at study entry. Deaths and their causes were documented throughout the study using various data sources. Marginal structural Cox proportional hazards models were used to evaluate the role of diet quality, as a time-varying covariate, on mortality. There were 93 deaths from all causes and 74 cancer-related deaths adjudicated throughout the observation period. There was a strong inverse association between adherence to the AHEI-2010, all-cause mortality (HRQ5–Q1:0.07, 95% CI:0.01–0.43, ptrend:0.04), and cancer-specific mortality (HRQ5–Q1:0.15, 95% CI:0.02–1.07, ptrend:0.04). Other more modest associations were noted for the low-carbohydrate indices. In sum, higher adherence to the AHEI-2010 and a plant-based low-carbohydrate index throughout the first 3 years since diagnosis may bolster survival and prognosis in newly diagnosed patients with HNSCC.

Much of the global nitrous oxide emissions are derived from agricultural management driving microbial N transformations. Crop rotation, no-till, and cover cropping are feasible conservation agronomic strategies used to prevent N losses to the environment, though their effect on soil microbial N cycling at the field scale remains relatively unknown. Our goal was to determine the effect of crop rotation (continuous corn [Zea mays L.], CCC; and continuous soybean [Glycine max (L.) Merr.], SSS), tillage (no-till, NT; and chisel tillage, T), and cover crops (cover crop mixture, CC; and no cover crop, NCC) on the quantification of functional genes related to the N cycle from different times throughout the growing season. The study was conducted during the growing season of the cash crops following the first season of cover crops introduced after 23 years of management. Using quantitative polymerase chain reaction (qPCR) techniques, we quantified nifH (N2 fixation), amoA (nitrification) and nirK, nirS, and nosZ (denitrification). Our results show that CCC increased nitrous oxide emissions by 44% compared to SSS and reduced soil pH by nearly 1 unit. The reduction in soil pH, coupled with an increase in fertilizer-derived ammonium, caused ammonia-oxidizing bacteria (AOB) and nirK copy numbers to increase. The SSS rotation showed opposite results. Bacterial denitrification via the nirK pathway was likely the N cycle mechanism behind nitrous oxide emissions in CCC. The cover crop mixture of cereal rye [Secale cereale L.] and hairy vetch [Vicia villosa Roth] reduced soil nitrate levels, though they did increase nitrous oxide emissions, likely due to priming and the inclusion of a legume in the cover crop mixture. Nitrous oxide emissions were affected by sampling date, crop rotation, and cover crop use, suggesting management factors that add abundantly available N alter the microbial N cycle directly or indirectly. Chisel tillage increased the abundance of all N cycle genes compared to no-till. Together, our work adds further insight into the microbial N cycle, especially nitrous oxide evolution, from three common conservation agricultural management practices, contributing to our understanding of key soil biogeochemical processes.

Abstract Background The aim of the study was to investigate the effect of energy overfeeding during the dry period on adipose tissue transcriptome profiles during the periparturient period in dairy cows. Methods Fourteen primiparous Holstein cows from a larger cohort receiving a higher-energy diet (1.62 Mcal of net energy for lactation/kg of dry matter; 15% crude protein) for ad libitum intake to supply 150% (OVR) or 100% (CTR) of energy requirements from dry off until parturition were used. After calving, all cows received the same lactation diet. Subcutaneous adipose tissue (SAT) biopsies were collected at − 14, 1, and 14 d from parturition (d) and used for transcriptome profiling using a bovine oligonucleotide microarray. Data mining of differentially expressed genes (DEG) between treatments and due to sampling time was performed using the Dynamic Impact Approach (DIA) and Ingenuity Pathway Analysis (IPA). Results There was a strong effect of over-feeding energy on DEG with 2434 (False discovery rate-corrected P

Weaning wields environmental, social, and nutritional stresses that are detectable in the blood metabolite levels of the offspring. Prenatal stress in the form of maternal immune activation (MIA) in response to infection, which is associated with health and behavior disorders, also elicits prolonged changes in blood and brain cytokine and metabolite levels of the offspring. The goal of this study was to investigate the effects of weaning and MIA on the offspring’s liver function to advance the understanding of the impact of stressors on peripheral and central nervous systems, physiology, and health. Gas chromatography–mass spectrometry analysis was used to compare the level of hepatic metabolites from 22-day-old pigs (n = 48) evenly distributed among weaning (nursed or weaned), viral MIA exposure (yes or no), and sexes. Weaning effects were detected on 38 metabolites at p-value < 0.05 (28 metabolites at FDR p-value < 0.05), and sex-dependent MIA effects were detected on 11 metabolites. Multiple intermediate and final products of the enriched (FDR p-value < 0.05) glycolysis and gluconeogenesis and pentose phosphate pathways were over-abundant in nursed relative to weaned pigs. The enriched pathways confirm the impact of weaning on hepatic metabolic shift, oxidative stress, and inflammation. Higher levels of the glucogenic amino acid histidine are observed in pigs exposed to MIA relative to controls, suggesting that the role of this metabolite in modulating inflammation may supersede the role of this amino acid as an energy source. The lower levels of cholesterol detected in MIA pigs are consistent with hypocholesterolemia profiles detected in individuals with MIA-related behavior disorders. Our findings underline the impact of weaning and MIA stressors on hepatic metabolites that can influence peripheral and central nervous system metabolic products associated with health and behavior disorders.

Although dietary fiber is not considered an essential nutrient in a complete and balanced diet for felines, it provides a substrate for fermentation by gut microbiota, thus promoting gastrointestinal health through the production of fermentative metabolites, as well as improving laxation. The aim of this research was to evaluate the novel fiber source, Miscanthus grass (Miscanthus giganteus), in comparison with traditional fiber sources and their effects on fecal quality, apparent total tract digestibility (ATTD), fecal fermentative end products, and microbiota of healthy adult cats. Four dietary treatments were evaluated, differing in dietary fiber source. The diets were formulated to meet or exceed the AAFCO (2018) nutritional profile for adult cats and contained either cellulose (CO), Miscanthus grass fiber (MF), a blend of Miscanthus fiber and tomato pomace (MF + TP), or beet pulp (BP). The study was conducted using a completely randomized design with 28 neutered adult, domesticated shorthair cats (19 females and 9 males, mean age 2.2 ± 0.03 years; mean body weight 4.6 ± 0.7 kg, mean body condition score 5.6 ± 0.6). The experimental period comprised 21 days, and a fresh fecal and a total fecal collection were performed during the last 4 days of the trial period. Daily food intake (DM basis) was similar across all groups (P > 0.05). Additionally, treatment did not affect fecal output (as-is or DM basis), fecal score, or fecal pH (P > 0.05). Cats fed BP had significantly higher total dietary fiber ATTD than all the other treatments (P < 0.05) and the highest concentrations of total short-chain fatty acid, acetate, and propionate (P < 0.05), while butyrate concentrations were similar for all treatments (P > 0.05). Inclusion of dietary fibers was effective in modulating gut microbiota. Cats fed diets containing Miscanthus grass had greater α-diversity than cats fed BP. As no adverse effects on health, fecal quality, or ATTD of macronutrients were observed with the inclusion of 9% Miscanthus grass fiber or fiber blend, the data suggest that Miscanthus grass fiber and fiber blends are viable alternatives to the traditional dietary fiber sources used in commercial extruded feline diets, being most comparable to cellulose.

The popularity of plant-based protein sources has increased as consumer demand for grain-free and novel protein sources increase. Minimal research has been conducted as regards to use of legumes and yeast and their effects on acceptability and digestibility in canine diets. The objective of this study was to evaluate macronutrient apparent total tract digestibility (ATTD), gastrointestinal tolerance, and fermentative end-products in extruded, canine diets. Five diets were formulated to be isocaloric and isonitrogenous with either garbanzo beans (GBD), green lentils (GLD), peanut flour (PFD), dried yeast (DYD), or poultry by-product meal (CON) as the primary protein sources. Ten adult, intact, female beagles (mean age: 4.2 ± 1.1 yr, mean weight: 11.9 ± 1.3 kg) were used in a replicated, 5 × 5 Latin square design with 14 d periods. Each experimental period consisted of 10 d of diet adaptation, followed by 4 d of total fecal and urine collection. A fasted, 5 ml blood sample was collected at the end of each period and analyzed for serum metabolites and complete blood count. Serum metabolites were within normal ranges and all dogs remained healthy throughout the study. Fecal quality, evaluated on a 5-point scale, was considered ideal. Macronutrient ATTD was similar among dietary treatments, with diets highly digestible (>80%). Total fecal branched-chain fatty acid concentrations were highest (P < 0.05) for DYD (23.4 μmol/g) than GLD (16.1 μmol/g) and PFD (16.0 μmol/g) but not different (P > 0.05) than other treatments. The plant-based protein treatments had greater (P < 0.05) total fecal short chain fatty acid (SCFA) concentrations (average 627.6 μmol/g) compared with CON (381.1 μmol/g). Fecal butyrate concentration was highest (P < 0.05) for DYD than all other dietary treatments (103.9 μmol/g vs. average 46.2 μmol/g). Fecal microbial communities showed Firmicutes, Bacteroidetes, Fusobacteria, and Proteobacteria as abundant phyla. There was greater β-diversity for dogs fed DYD which differed from all other diets in both weighted and unweighted UNIFRAC analyses. Inclusion of these novel, plant-based, protein sources showed no detrimental effects on nutrient digestibility or fecal characteristics and represent viable protein sources in canine diets that can produce beneficial shifts in fecal metabolites.

The research objectives were to evaluate the effect of dietary supplementation of white (WSH) and red (RSH) sorghum grains on gastrointestinal health of felines through the determination of apparent total tract macronutrient digestibility (ATTD), fecal characteristics, fermentative end-products, and microbiota, compared with a traditional corn-based diet. We hypothesize that inclusion of RSH and WSH, respectively, would be well-accepted by cats, and the RSH and WSH diets would be comparable to corn when added as the main carbohydrate source in extruded diets. Three diets containing 30% corn, 30% WSH, or 30% RSH were formulated to meet or exceed the AAFCO (2018) nutrient profiles for cats during growth. Nine male cats (0.8 ± 0.00 yr) were randomly assigned to one of the three dietary treatments using a triplicated 3 × 3 Latin square design. Experimental periods consisted of 14 d (10 d of diet adaption and 4 d of total and fresh fecal collections). The ATTD of dry matter (DM) did not differ amongst treatments, organic matter was greatest (P < 0.05) for both sorghum diets (86.4%) and lowest for the corn diet (84.2%), crude protein was comparable among diets ranging from 84.5 to 86.6%, acid hydrolyzed fat was high among diets varying between 91.4 and 92.8%, and total dietary fiber was greatest (P < 0.05) for the WSH diet (56.0%) with the corn diet being lowest (44.7%). Digestible energy was greatest (P < 0.05) for the WSH diet (4.66 kcal/g) and lowest for the corn diet (4.54 kcal/g), with the RSH diet being intermediate (4.64; P > 0.05). Fecal pH (6.3–6.5) and most fecal metabolites did not differ among diets except for phenol/indole concentrations that were significantly lower (P < 0.05) in cats fed the RSH diet (1.5 μmole/g DM) than for cats fed the corn diet (2.1 μmole/g DM). Bacteroidetes, Firmicutes, Fusobacteria, and Proteobacteria were the major phyla observed in the microbiota of feces of cats fed the three experimental diets, with no differences seen amongst all treatments. Data indicate that dietary supplementation of these varieties of WSH and RSH as carbohydrate sources were well-tolerated by the cat.

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.

Cover cropping (CC) is the most promising in-field practice to improve soil health and mitigate N losses from fertilizer use. Although the soil microbiota play essential roles in soil health, their response to CC has not been well characterized by bioindicators of high taxonomic resolution within typical agricultural systems. Our objective was to fill this knowledge gap with genus-level indicators for corn [Zea mays L.] monocultures with three N fertilizer rates (N0, N202, N269; kg N ha−1), after introducing a CC mixture of cereal rye [Secale cereale L.] and hairy vetch [Vicia villosa Roth.], using winter fallows (BF) as controls. A 3 × 2 split-plot arrangement of N rates and CC treatments was studied in a randomized complete block design with three replicates over two years. Bacterial and archaeal 16S rRNA and fungal ITS regions were sequenced with Illumina MiSeq system. Overall, our high-resolution bioindicators were able to represent specific functional or ecological shifts within the microbial community. The abundances of indicators representing acidophiles, nitrifiers, and denitrifiers increased with N fertilization, while those of heterotrophic nitrifiers, nitrite oxidizers, and complete denitrifiers increased with N0. Introducing CC decreased soil nitrate levels by up to 50% across N rates, and CC biomass increased by 73% with N fertilization. CC promoted indicators of diverse functions and niches, including N-fixers, nitrite reducers, and mycorrhizae, while only two N-cycling genera were associated with BF. Thus, CC can enhance the soil biodiversity of simplified cropping systems and reduce nitrate leaching, but might increase the risk of nitrous oxide emission without proper nutrient management. This primary information is the first of its kind in this system and provided valuable insights into the limits and potential of CC as a strategy to improve soil health.

Migraine is often accompanied by exacerbated sensitivity to stimuli and pain associated with alternative splicing of genes in signaling pathways. Complementary analyses of alternative splicing of neuropeptide prohormone and receptor genes involved in cell–cell communication in the trigeminal ganglia and nucleus accumbens regions of mice presenting nitroglycerin-elicited hypersensitivity and control mice were conducted. De novo sequence assembly detected 540 isoforms from 168 neuropeptide prohormone and receptor genes. A zero-inflated negative binomial model that accommodates for potential excess of zero isoform counts enabled the detection of 27, 202, and 12 differentially expressed isoforms associated with hypersensitivity, regions, and the interaction between hypersensitivity and regions, respectively. Skipped exons and alternative 3′ splice sites were the most frequent splicing events detected in the genes studied. Significant differential splicing associated with hypersensitivity was identified in CALCA and VGF neuropeptide prohormone genes and ADCYAP1R1, CRHR2, and IGF1R neuropeptide receptor genes. The prevalent region effect on differential isoform levels (202 isoforms) and alternative splicing (82 events) were consistent with the distinct splicing known to differentiate central nervous structures. Our findings highlight the changes in alternative splicing in neuropeptide prohormone and receptor genes associated with hypersensitivity to pain and the necessity to target isoform profiles for enhanced understanding and treatment of associated disorders such as migraine.

The combined effects on pig behavior of maternal immune challenge during gestation followed by a second immune challenge later in life have not been studied. Porcine reproductive and respiratory syndrome virus (PRRSV) infection during gestation can elicit maternal immune activation (MIA) yet the interactions with the offspring response to a second immune challenge after birth remains unexplored. Knowledge on the response to viral challenges in rodents has been gained through the use of the viral mimetic polyinosinic-polycytidylic acid (Poly(I:C)), yet the effects of this immune stimulant on pig behavior have not been assessed. This study advances the understanding of the combined effect of MIA and a second immune challenge later in life on female and male pig behavior. Three complementary experiments enabled the development of an effective Poly(I:C) challenge in pigs, and testing the interaction between PRRSV-elicited MIA, Poly(I:C) challenge at 60 days of age, and sex on behaviors. Individual-level observations on sickness, locomotor, and social behaviors were measured 1–3 h after Poly(I:C) challenge. Vomiting, panting, lethargy, walking, laying, playing, and touching behaviors were analyzed using generalized linear mixed effect models. Results indicated that a Poly(I:C) dose of 1 mg/kg within 1 h after injection increased the incidence of laying and sickness behavior. The Poly(I:C) challenge decreased the incidence of locomotor behaviors and activity levels. Pigs exposed to MIA had lower rates of social behaviors such as playing. The combined effect of PRRSV-elicited MIA and Poly(I:C) immune challenge further sensitized the pigs to behavior disruption across sexes including changes in sternal and lateral laying, walking, lethargy, and touching incidence. Notably, the effects of Poly(I:C) immune challenge alone on behaviors tended to be more extreme in males, whereas the effects of Poly(I:C) following MIA tended to be more extreme in females. Our findings demonstrate that MIA and Poly(I:C) affected behaviors, and the viral mimetic effects shortly after injection can offer insights into the prolonged effect of postnatal viral infections on feeding, social interactions and health status. Management practices that reduce the likelihood of gestational diseases and accommodate for behavioral disruptions in the offspring can minimize the impact of MIA.

The prolonged and sex-dependent impact of maternal immune activation (MIA) during gestation on the molecular pathways of the amygdala, a brain region that influences social, emotional, and other behaviors, is only partially understood. To address this gap, we investigated the effects of viral-elicited MIA during gestation on the amygdala transcriptome of pigs, a species of high molecular and developmental homology to humans. Gene expression levels were measured using RNA-Seq on the amygdala for 3-week-old female and male offspring from MIA and control groups. Among the 403 genes that exhibited significant MIA effect, a prevalence of differentially expressed genes annotated to the neuroactive ligand–receptor pathway, glutamatergic functions, neuropeptide systems, and cilium morphogenesis were uncovered. Genes in these categories included corticotropin-releasing hormone receptor 2, glutamate metabotropic receptor 4, glycoprotein hormones, alpha polypeptide, parathyroid hormone 1 receptor, vasointestinal peptide receptor 2, neurotensin, proenkephalin, and gastrin-releasing peptide. These categories and genes have been associated with the MIA-related human neurodevelopmental disorders, including schizophrenia and autism spectrum disorders. Gene network reconstruction highlighted differential vulnerability to MIA effects between sexes. Our results advance the understanding necessary for the development of multifactorial therapies targeting immune modulation and neurochemical dysfunction that can ameliorate the effects of MIA on offspring behavior later in life.

Weaning stress can elicit changes in the metabolic, hormone and immune systems of pigs and interact with prolonged disruptions stemming from maternal immune activation (MIA) during gestation. The present study advances the characterization of the combined effects of weaning stress and MIA on blood chemistry, immune and hormone indicators that inform on the health of pigs. Three-week-old female and male offspring of control gilts or gilts infected with the porcine reproductive and respiratory syndrome virus were allocated to weaned or nursed groups. The anion gap and bilirubin profiles suggest that MIA enhances tolerance to the effects of weaning stress. Interleukin 1 beta and interleukin 2 were highest among weaned MIA females, and cortisol was higher among weaned relative to nursed pigs across sexes. Canonical discriminant analysis demonstrated that weaned and nursed pigs have distinct chemistry profiles, whereas MIA and control pigs have distinct cytokine profiles. The results from this study can guide management practices that recognize the effects of the interaction between MIA and weaning stress on the performance and health of pigs.

The pharmacological agent nitroglycerin (NTG) elicits hyperalgesia and allodynia in mice. This model has been used to study the neurological disorder of trigeminovascular pain or migraine, a debilitating form of hyperalgesia. The present study validates hyperalgesia in an established mouse model of chronic migraine triggered by NTG and advances the understanding of the associated molecular mechanisms. The RNA-seq profiles of two nervous system regions associated with pain, the trigeminal ganglia (TG) and the nucleus accumbens (NAc), were compared in mice receiving chronic NTG treatment relative to control (CON) mice. Among the 109 genes that exhibited an NTG treatment-by-region interaction, solute carrier family 32 (GABA vesicular transporter) member 1 (Slc32a1) and preproenkephalin (Penk) exhibited reversal of expression patterns between the NTG and CON groups. Erb-b2 receptor tyrosine kinase 4 (Erbb4) and solute carrier family 1 (glial high affinity glutamate transporter) member 2 (Slc1a2) exhibited consistent differential expression between treatments across regions albeit at different magnitude. Period circadian clock 1 (Per1) was among the 165 genes that exhibited significant NTG treatment effect. Biological processes disrupted by NTG in a region-specific manner included adaptive and innate immune responses; whereas glutamatergic and dopaminergic synapses and rhythmic process were disrupted in both regions. Regulatory network reconstruction highlighted the widespread role of several transcription factors (including Snrnp70, Smad1, Pax6, Cebpa, and Smpx) among the NTG-disrupted target genes. These results advance the understanding of the molecular mechanisms of hyperalgesia that can be applied to therapies to ameliorate chronic pain and migraine.

The effects of maternal immune activation (MIA) elicited by a prenatal stressor and postnatal metabolic or immune stressors on chemical and inflammatory biomarkers were studied in male and female pigs. Pigs exposed to MIA elicited by porcine reproductive and respiratory syndrome virus and matching controls were assigned at two months of age to fasting stress, immune stress, or a saline group. The serum levels of over 30 chemistry and immune analytes were studied. Significantly low levels of blood urea nitrogen were detected in females exposed to MIA, while the highest creatinine levels were identified in fasting females exposed to MIA. The levels of interferon gamma and interleukin 8 were highest in pigs exposed to postnatal immune challenge. The profiles suggest that MIA may sensitize pigs to postnatal stressors for some indicators while making them more tolerant of other stressors. Effectiveness of practices to ameliorate the impact of postnatal stressors on the physiology of the pig could be enhanced by considering the prenatal stress circumstances.

Offspring born to dams genetically tested for resistance to fescue toxicity were separated in groups based on their dams’ resistance level (tolerant vs. susceptible). Rumen-protected niacin (RPN) is proposed as a potential alleviator for vasoconstriction produced by fescue toxicity. Complete blood count (CBC) analysis was utilized for detection of significant responses to treatments applied. Our objectives were as follows: (a) to analyze changes in CBC due to fescue toxicity, maternal resistance level, and RPN in growing offspring; and (b) to assess the effects of maternal resistance level when consuming endophyte-infected tall fescue seeds in addition to RPN in offspring performance. Body weight, average daily gain, or health status were not improved by RPN or the genetic test to detect fescue toxicity resistance. Typical signs of alkaloids intoxication and heat stress were noticed in offspring. Particularly, rectal temperature was greater for susceptible control heifers. Results showed that susceptible control offspring presented signs of anemia denoted by low mean corpuscular hemoglobin (MCH) and mean corpuscular volume (MCV). High levels of white blood cells (WBC) and basophils in combination to low neutrophils to lymphocytes ratio were the signs of infection or inflammation detected in the CBC analysis, especially in tolerant niacin steers. Furthermore, offspring of control heifers had a greater percentage of reticulocytes and RDW, denoting signs of anemia.

Exogenous trans-10, cis-12-CLA (CLA) reduces lipid synthesis in murine adipose and mammary (MG) tissues. However, genomewide alterations in MG and liver (LIV) associated with dietary CLA during lactation remain unknown. We fed mice (n=5/diet) control or control + trans-10, cis-12-CLA (37 mg/day) between d 6 and d 10 postpartum. The 35,302 annotated murine exonic evidence-based oligo (MEEBO) microarray and quantitative RT-PCR were used for transcript profiling. Milk fat concentration was 44% lower on d 10 versus d 6 due to CLA. The CLA diet resulted in differential expression of 1,496 genes. Bioinformatics analyses underscored that a major effect of CLA on MG encompassed alterations in cellular signaling pathways and phospholipid species biosynthesis. Dietary CLA induced genes related to ER stress (Xbp1), apoptosis (Bcl2), and inflammation (Orm1, Saa2, and Cp). It also induced marked inhibition of PPARγ signaling, including downregulation of Pparg and Srebf1 and several lipogenic target genes (Scd, Fasn, and Gpam). In LIV, CLA induced hepatic steatosis probably through perturbations in the mitochondrial functions and induction of ER stress. Overall, results from this study underscored the role of PPARγ signaling on mammary lipogenic target regulation. The proinflammatory effect due to CLA could be related to inhibition of PPARγ signaling.