Selected Grantee Publications
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- 138 results found
- Neurological
- Pediatrics
Adverse Biobehavioral Effects in Infants Resulting from Pregnant Rhesus Macaques’ Exposure to Wildfire Smoke
Capitanio et al., Nature Communications. 2022.
https://www.doi.org/10.1038/s41467-022-29436-9
Exposure to wildfire smoke (WFS) is a growing health concern as wildfires increase in number and size due to climate change. Researchers found that developing rhesus monkeys exposed to WFS from the Camp Fire in California (November 2018) during the first third of gestation exhibited greater inflammation, blunted cortisol, more passive behavior, and memory impairment compared to animals conceived after smoke had dissipated. Analysis of a historical control cohort did not support the alternative hypothesis that conception timing alone explained the results. These findings suggest that WFS may have a teratogenic effect on neural development in the primate fetus. Supported by ORIP (P51OD011107, R24OD010962) and NIEHS.
Early Post-Vaccination Gene Signatures Correlate With the Magnitude and Function of Vaccine-Induced HIV Envelope–Specific Plasma Antibodies in Infant Rhesus Macaques
Vijayan et al., Frontiers in Immunology. 2022.
https://www.doi.org/10.3389/fimmu.2022.840976
An effective vaccine is needed to reduce HIV infections, particularly among younger people. The initiation of an HIV vaccine regimen in early life could allow the development of mature HIV‑specific antibody responses that protect against infection. The investigators compared the effects of two vaccine regimens in infant rhesus macaques (sex not specified). Both vaccines induced a rapid innate response, indicated by elevated inflammatory plasma cytokines and altered gene expression. By performing a network analysis, the investigators identified differentially expressed genes associated with B cell activation. These findings suggest that vaccine-induced immunity can be optimized by modulating specific antibody and T cell responses. Supported by ORIP (P51OD011107), NCI, NIAID, and NIDCR.
A Potent Myeloid Response Is Rapidly Activated in the Lungs of Premature Rhesus Macaques Exposed to Intra-Uterine Inflammation
Jackson et al., Mucosal Immunology. 2022.
https://www.doi.org/10.1038/s41385-022-00495-x
Up to 40% of preterm births are associated with histological chorioamnionitis (HCA), which can lead to neonatal mortality, sepsis, respiratory disease, and neurodevelopmental problem. Researchers used rhesus macaques to comprehensively describe HCA-induced fetal mucosal immune responses and delineate the individual roles of IL-1β and TNFα in HCA-induced fetal pathology. Their data indicate that the fetal innate immune system can mount a rapid, multifaceted pulmonary immune response to in utero exposure to inflammation. Taken together, this work provides mechanistic insights into the association between HCA and the postnatal lung morbidities of the premature infant and highlights the therapeutic potential of inflammatory blockade in the fetus. Supported by ORIP (P51OD011107), NIEHS, NIDDK, NHLBI, and NICHD.
Inflammatory Blockade Prevents Injury to the Developing Pulmonary Gas Exchange Surface in Preterm Primates
Toth et al., Science Translational Medicine. 2022.
https://www.doi.org/10.1126/scitranslmed.abl8574
Chorioamnionitis, an inflammatory condition affecting the placenta and fluid surrounding the developing fetus, affects 25% to 40% of preterm births. Investigators used a prenatal rhesus macaque model to assess how fetal inflammation could affect lung development. They found that inflammatory injury directly disrupted the developing gas exchange surface of the primate lung, with extensive damage to alveolar structure. Blockade of the inflammatory cytokines IL-1β and TNFα ameliorated LPS-induced inflammatory lung injury by blunting stromal responses to inflammation and modulating innate immune activation in myeloid cells. These data provide new insight into key mechanisms of developmental lung injury and highlight targeted inflammatory blockade as a potential therapeutic approach to ameliorate lung injury in the neonatal population. Supported by ORIP (P51OD011107), NIAID, NHLBI, NICHD, and NIEHS.
The Early Life Microbiota Mediates Maternal Effects on Offspring Growth in a Nonhuman Primate
Petrullo et al., iScience. 2022.
https://www.doi.org/10.1016/j.isci.2022.103948
Mammalian mothers influence offspring development by providing nutrients and other bioactive compounds through the placenta or milk. A relatively unexplored mechanism for maternal effects is vertical transmission of bacteria through milk to the infant gut. Infants that receive more glycan-utilizing bacteria from milk might better exploit oligosaccharides, which could improve nutrition and accelerate growth. Researchers found that first-time vervet mothers harbored a milk bacterial community that was less diverse due to the dominance of Bacteroides fragilis, a glycan-utilizing bacteria. These low-parity females had infants that grew faster, suggesting that vertical transmission of bacteria via milk can mediate maternal effects on growth. These results indicate non-nutritive milk constituents play important roles in development. Commercial milk formula might need to be improved or supplemented to better support infant health. Supported by ORIP (P40OD010965) and NCATS.
Functional and Ultrastructural Analysis of Reafferent Mechanosensation in Larval Zebrafish
Odstrcil et al., Current Biology. 2022.
https://www.sciencedirect.com/science/article/pii/S096098222101530X
All animals need to differentiate between exafferent stimuli (caused by the environment) and reafferent stimuli (caused by their own movement). Researchers characterized how hair cells in zebrafish larvae discriminate between reafferent and exafferent signals. Dye labeling of the lateral line nerve and functional imaging was combined with ultra-structural electron microscopy circuit reconstruction to show that cholinergic signals originating from the hindbrain transmit efference copies, and dopaminergic signals from the hypothalamus may affect threshold modulation. Findings suggest that this circuit is the core implementation of mechanosensory reafferent suppression in these young animals. Supported by ORIP (R43OD024879, R44OD024879) and NINDS.
Heritability of Social Behavioral Phenotypes and Preliminary Associations with Autism Spectrum Disorder Risk Genes in Rhesus Macaques: A Whole Exome Sequencing Study
Gunter et al., Autism Research. 2022.
https://onlinelibrary.wiley.com/doi/full/10.1002/aur.2675
Investigators quantified individual variation in social interactions among juvenile rhesus macaques of both sexes using both a standard macaque ethogram (a catalogue of animal behavior over time) and a macaque-relevant modification of the human Social Responsiveness Scale to study genetic influences on key aspects of social behavior and interactions. The analyses demonstrate that various aspects of juvenile social behavior exhibit significant genetic heritability, with quantitative genetic effects similar to autism spectrum disorder (ASD) in human children. The significant genetic and sequencing data may be used to examine potential genetic associations with human ASD. Supported by ORIP (P51OD011132), NHGRI and NIMH.
Reduced Infant Rhesus Macaque Growth Rates Due to Environmental Enteric Dysfunction and Association with Histopathology in the Large Intestine
Hendrickson et al., Nature Communications. 2022.
https://www.doi.org/10.1038/s41467-021-27925-x
Researchers characterized environmental enteric (relating to the intestines) dysfunction (EED) among infant rhesus macaques (n=80, both sexes) naturally exposed to enteric pathogens commonly linked to human growth stunting. Despite atrophy and abnormalities observed in the small intestine, poor growth trajectories and low serum tryptophan (an amino acid needed for protein and enzymes) levels were correlated with increased histopathology (microscopic tissue examination for disease manifestation) in the large intestine. This study provides insight into the mechanisms underlying EED and indicates that the large intestine may be an important target for therapeutic intervention. Supported by ORIP (P51OD011092, P51OD011107) and NIGMS.
Neuroinflammatory Profiling in SIV-Infected Chinese-Origin Rhesus Macaques on Antiretroviral Therapy
Solis-Leal et al., Viruses. 2022.
https://www.doi.org/10.3390/v14010139
The central nervous system (CNS) HIV reservoir contributes to residual neuroimmune activation, which can lead to HIV-associated neurocognitive disorder. Researchers characterized the expression of signaling molecules associated with inflammation in plasma, cerebrospinal fluid, and basal ganglia of Chinese-origin rhesus macaques (sex not specified) with simian immunodeficiency virus (SIV). They reported a correlation between levels of CCL2 in plasma and cerebrospinal fluid, suggesting that researchers could infer the degree of CNS inflammation by testing CCL2 levels in peripheral blood. Overall, these findings provide insight into neuroinflammation and signaling associated with HIV persistence in the CNS. Supported by ORIP (P51OD011104, P51OD011133), NIMH, and NINDS.
Complement Blockade in Recipients Prevents Delayed Graft Function and Delays Antibody-mediated Rejection in a Nonhuman Primate Model of Kidney Transplantation
Eerhart et al., Transplantation. 2022.
Investigators evaluated the efficacy of a high-dose recombinant human C1 esterase inhibitor (rhC1INH) in preventing delayed graft function (DGF) in a rhesus macaque (RM) model for kidney transplantation after brain death and prolonged cold ischemia. The majority (4 of 5) of vehicle-treated recipients developed DGF, whereas DGF was observed in only 1 of 8 rhC1INH-treated recipients. RMs treated with rhC1INH also had faster creatine recovery, superior urinary output, and reduced biomarkers of allograft injury for the first week. The results suggest high-dose C1INH treatment in transplant recipients is an effective strategy to reduce kidney injury and inflammation, prevent DGF, delay antibody-mediated rejection development, and improve transplant outcomes. Supported by ORIP (P51OD011106), NIAID, and NIDDK.