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Global metabolic profiles in a non-human primate model of maternal immune activation: implications for neurodevelopmental disorders

Boktor, Joseph C. and Adame, Mark D. and Rose, Destanie R. and Schumann, Cynthia M. and Murray, Karl D. and Bauman, Melissa D. and Careaga, Milo and Mazmanian, Sarkis K. and Ashwood, Paul and Needham, Brittany D. (2022) Global metabolic profiles in a non-human primate model of maternal immune activation: implications for neurodevelopmental disorders. Molecular Psychiatry, 27 (12). pp. 4959-4973. ISSN 1359-4184. PMCID PMC9772216. doi:10.1038/s41380-022-01752-y. (In Press)

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Epidemiological evidence implicates severe maternal infections as risk factors for neurodevelopmental disorders, such as ASD and schizophrenia. Accordingly, animal models mimicking infection during pregnancy, including the maternal immune activation (MIA) model, result in offspring with neurobiological, behavioral, and metabolic phenotypes relevant to human neurodevelopmental disorders. Most of these studies have been performed in rodents. We sought to better understand the molecular signatures characterizing the MIA model in an organism more closely related to humans, rhesus monkeys (Macaca mulatta), by evaluating changes in global metabolic profiles in MIA-exposed offspring. Herein, we present the global metabolome in six peripheral tissues (plasma, cerebrospinal fluid, three regions of intestinal mucosa scrapings, and feces) from 13 MIA and 10 control offspring that were confirmed to display atypical neurodevelopment, elevated immune profiles, and neuropathology. Differences in lipid, amino acid, and nucleotide metabolism discriminated these MIA and control samples, with correlations of specific metabolites to behavior scores as well as to cytokine levels in plasma, intestinal, and brain tissues. We also observed modest changes in fecal and intestinal microbial profiles, and identify differential metabolomic profiles within males and females. These findings support a connection between maternal immune activation and the metabolism, microbiota, and behavioral traits of offspring, and may further the translational applications of the MIA model and the advancement of biomarkers for neurodevelopmental disorders such as ASD or schizophrenia.

Item Type:Article
Related URLs:
URLURL TypeDescription ReadCube access
Boktor, Joseph C.0000-0003-2456-1913
Schumann, Cynthia M.0000-0002-3763-7596
Murray, Karl D.0000-0001-8159-6843
Bauman, Melissa D.0000-0003-0701-3851
Careaga, Milo0000-0002-5944-7048
Mazmanian, Sarkis K.0000-0003-2713-1513
Ashwood, Paul0000-0002-4255-1893
Needham, Brittany D.0000-0002-0280-1886
Additional Information:We thank the veterinary and animal services staff of the CNPRC for care of the animals. Poly ICLC was kindly provided by Dr. Andres Salazar, MD, Oncovir, Washington D.C. This work was supported by grants from Autism Speaks (Grant #7567 to PA, and SKM); the Johnson Foundation (to PA); the Brain Foundation (to PA and to SKM); NARSAD Foundation (to PA); Axial Biotherapeutics (to SKM); and the National Institutes of Health (HD090214 to PA) and (MH100556 to SKM). Development of the animal model was supported by a grant from the Simons Foundation to the late Dr. Paul Patterson (SFARI 9900060), with additional support provided by the base grant (RR00169) of the California National Primate Research Center (CNPRC), a gift from Ted and Ginger Jenkins and a UC Davis RISE Award (to PA and MB). Contributions. MDB, CMS, KDM, and MC worked directly with the NHPs and collected samples. DRR performed immune profiling. JCB, MDA, and BDN analyzed metabolomics data and wrote the manuscript. SKM, PA and MDB secured funding for the project. All authors edited the manuscript. Code availability. Scripts for data-visualization and statistical analysis of correlations, pathway enrichment, and microbiome analysis are available at: COMPETING INTERESTS. SKM has financial interest in Axial Biotherapeutics. JCB, MDA, DRR, CMS, KDM, MDB, MC, PA, and BDN report no financial conflicts of interest.
Group:Tianqiao and Chrissy Chen Institute for Neuroscience
Funding AgencyGrant Number
Autism Speaks7567
Johnson FoundationUNSPECIFIED
Brain FoundationUNSPECIFIED
Brain and Behavior Research FoundationUNSPECIFIED
Axial BiotherapeuticsUNSPECIFIED
Simons FoundationSFARI 9900060
California National Primate Research CenterRR00169
Ted and Ginger JenkinsUNSPECIFIED
University of California, DavisUNSPECIFIED
Issue or Number:12
PubMed Central ID:PMC9772216
Record Number:CaltechAUTHORS:20221206-014213741
Persistent URL:
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:118250
Deposited By: Yvette Garcia-Flores
Deposited On:07 Dec 2022 18:56
Last Modified:11 Apr 2023 15:48

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