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Neonatal brain development can be disrupted by infection that results in microglial cell activation and neuroinflammation. Studies indicate that polyunsaturated fatty acids (PUFAs) and their metabolites can resolve inflammation. It is not known if dietary PUFA increases lipid metabolites in brain or reduces neuroinflammation in neonates. We hypothesized that dietary PUFAs might suppress neuroinflammation by inhibiting pro-inflammatory cytokine over-production and promoting inflammatory resolution in the periphery and brain. Piglets were obtained on postnatal day (PD) 2 and randomly assigned to herring roe oil (HRO) or control (CON) diet. HRO was included at 2 g/kg powdered diet. HRO increased DHA levels in occipital lobe and the DHA to arachidonic acid (ARA) ratio in hippocampal tissue. HRO decreased ARA metabolites in occipital lobe. HRO failed to attenuate microglial pro-inflammatory cytokine production ex vivo. HRO did not affect fever or circulating resolvin D1 levels. HRO decreased circulating neutrophils and liver inflammatory gene expression, but increased resolution marker gene expression in liver post LPS. HRO upregulated CXCL16, TGFBR1, and C1QA in microglial cells. HRO supplementation exerted beneficial effects on inflammation in the periphery, but further studies are needed to evaluate the specific effects of omega-3 supplementation on microglial cell physiology in the neonate.

Background: Intrauterine growth restriction is a common cause of small for gestational age (SGA) infants worldwide. SGA infants are deficient in digestive enzymes required for fat digestion and absorption compared to appropriate for gestational age (AGA) infants, putting them at risk for impaired neurocognitive development. Objective: The objective was to determine if a hydrolyzed fat (HF) infant formula containing soy free fatty acids, 2-monoacylglycerolpalmitate, cholesterol, and soy lecithin could increase brain tissue incorporation of essential fatty acids or white matter to enhance brain development in SGA and AGA neonatal piglet models. Methods: Sex-matched, littermate pairs of SGA (0.5–0.9 kg) and AGA (1.2–1.8 kg) 2 days old piglets (N = 60) were randomly assigned to control (CON) or HF formula diets in a 2 × 2 factorial design. On day 14, 24 piglets were used for hippocampal RNA-sequencing; the rest began a spatial learning task. On days 26–29, brain structure was assessed by magnetic resonance imaging (MRI). Cerebellum and hippocampus were analyzed for fatty acid content. Results: SGA piglets grew more slowly than AGA piglets, with no effect of diet on daily weight gain or weight at MRI. HF diet did not affect brain weight. HF diet increased relative volumes of 7 brain regions and white matter (WM) volume in both SGA and AGA piglets. However, HF did not ameliorate SGA total WM integrity deficits. RNA sequencing revealed SGA piglets had increased gene expression of synapse and cell signaling pathways and decreased expression of ribosome pathways in the hippocampus compared to AGA. HF decreased expression of immune response related genes in the hippocampus of AGA and SGA piglets, but did not correct gene expression patterns in SGA piglets. Piglets learned the T-maze task at the same rate, but SGA HF, SGA CON, and AGA HF piglets had more accurate performance than AGA CON piglets on reversal day 2. HF increased arachidonic acid (ARA) percentage in the cerebellum and total ARA in the hippocampus. Conclusions: HF enhanced brain development in the neonatal piglet measured by brain volume and WM volume in specific brain regions; however, more studies are needed to assess long-term outcomes.

Nicotine and acetylcholine cause immunosuppresion by signaling to the α7 nicotinic acetylcholine receptor (α7 nAChR) on immune cells. Neonicotinoids are nAChR agonists and widly used insecticides. We aimed to define the immunosuppressive potential of dietary exposure to the neonicotinoid imidacloprid (IMI) on the generation of innate and adaptive immune responses to porcine reproductive and respiratory syndrome virus (PRRSV). Piglets were randomized into groups based on diet and infection. Behavioral signs of illness were recorded. Urine IMI levels were measured by high performance liquid chromatography-mass spectrometry. Flow cytometry was used to determine the expression pattern of the α7 nAChR on porcine leukocytes as well as the effects of infection and treatment on circulating leukocyte populations. Serum cytokines and PRRSV-specific antibody levels were determined by ELISA. Viral RNA in lung, spleen and plasma was determined by RT-qPCR. Pigs in the treatment group had elevated urine levels of IMI. Treatment with IMI reduced body weight, caused bouts of hypothermia, increased serum IL-10 and elevated levels of virus-specific antibodies. Viral RNA levels in the spleen showed a trend toward being increased in pigs fed IMI. Our data indicates that IMI injection may modulate virus specific immune function during PRRSV infection.

During the postnatal period the developing brain is vulnerable to insults including nutrient insufficiency and infection that may lead to disrupted development and cognitive dysfunction. Since iron deficiency (ID) often presents with immunodeficiency, the objective of this study was to investigate peripheral viremia and inflammation as well as brain microglial phenotype and function when ID and respiratory infection occur simultaneously in a neonatal piglet model. On postnatal day 2 (PD 2) male and female piglets were assigned to one of four treatments and fed either control or ID milk replacer. On PD 8 half the pigs on each diet were inoculated with either vehicle or porcine reproductive and respiratory syndrome virus (PRRSV; P-129). Blood samples were collected prior to inoculation (PD 7) and repeated once weekly. Rectal temperature, feeding score, and sickness behavior were measured daily until PD 28. Hematocrit, hemoglobin, and serum iron were reduced by ID but not PRRSV infection. PRRSV-infected piglets displayed viremia by PD 14; however, those fed control diet had lower viral titer on PD 28, while circulating virus remained elevated in those fed an ID diet, suggesting that ID either impaired immune function necessary for viral clearance or increased viral replication. ID piglets infected with PRRSV displayed reduced sickness behavior compared to those fed control diet on PD 13-15 and 18-20. While ID piglet sickness behavior progressively worsened, piglets fed control diet displayed improved sickness score after PD 21. Microglia isolated from PRRSV piglets had increased MHCII expression and phagocytic activity ex vivo compared to uninfected piglets. ID did not alter microglial activation or phagocytic activity. Similarly, microglial cytokine expression was increased by PRRSV but unaffected by ID, in stark contrast to peripheral blood mononuclear cell (PBMC) cytokine expression, which was increased by infection and generally decreased by ID. Taken together, these data suggest that ID decreases peripheral immune function leading to increased viremia, but immune activity in the brain is protected from acute ID.

Background: Cognitive deficits associated with postnatal iron deficiency (ID) suggest abnormal brain development, but little is known about animals with gyrencephalic brains. Objective: The objective was to assess the impact of ID on brain development in piglets. Methods: Male and female Yorkshire piglets were reared from postnatal day (PD) 2 until PD 29 or 30 by using milk replacer adequate [control (CON)] or deficient (100 compared with 10 mg/kg) in iron and subjected to MRI to assess brain macrostructure, microstructure, and metabolites in the dorsal hippocampi and intervening space. After MRI, brains were collected for histology. Hematocrit, hemoglobin, and liver iron were measured to determine iron status. Results: Hematocrit and hemoglobin in ID piglets were less than CON after PD 14 (P < 0.001), and at the study end liver iron in ID piglets was less than CON (P < 0.001). Brain region volumes were not affected by ID, but changes in brain composition were evident. ID piglets had less white matter in 78,305 voxels, with large clusters in the hippocampus and cortex. ID piglets had less gray matter in 13,625 voxels primarily in cortical areas and more gray matter in 28,017 voxels, most notably in olfactory bulbs and hippocampus. The major effect of ID on white matter was supported by lower fractional anisotropy values in the corpus callosum (0.300 compared with 0.284, P = 0.006) and in whole brain white matter (0.313 compared with 0.307, P = 0.002) in ID piglets. In coronal brain sections, corpus callosum width was less (P = 0.043) in ID piglets. Inositol was lower (P = 0.01) and phosphocholine was higher (P = 0.03) in hippocampus of ID piglets. Conclusions: Postnatal ID in piglets affects brain development, especially white matter. If the effects of ID persist, it might explain the lasting detrimental effects on cognition.