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BACE1-Deficient Mice Exhibit Alterations in Immune System Pathways

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Abstract

BACE1 encodes for the beta-site amyloid precursor protein cleaving enzyme 1 or β-secretase. Genetic deletion of Bace1 leads to behavioral alterations and affects midbrain dopaminergic signaling and memory processes. In order to further understand the role of BACE1 in brain function and behavior, we performed microarray transcriptome profiling and gene pathway analysis in the hippocampus of BACE1-deficient mice compared to wild type. We identified a total of 91 differentially expressed genes (DEGs), mostly enriched in pathways related to the immune and inflammation systems, particularly IL-9 and NF-κB activation pathways. Serum levels of IL-9 were elevated in BACE1-deficient mice. Our network analysis supports an intimate connection between immune response via NF-κB and BACE1 signaling through the NRG1/Akt1 pathway. Our findings warrant future mechanistic studies to determine if BACE1 signaling and the IL-9 pathway interact to alter behavior and brain function. This study opens new avenues in the investigation of hippocampus-related neuroimmunological and neuroinflammation-associated disorders.

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Acknowledgments

This work was supported in by a NARSAD Brain and Behavior Research Young Investigator award to CWB.

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Authors and Affiliations

  1. Translational Psychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA

    L. Stertz, N. Monroy-Jaramillo & C. Walss-Bass

  2. Department of Biological Sciences, Saint Mary’s University, San Antonio, TX, USA

    V. Contreras-Shannon

  3. Department of Genetics, National Institute of Neurology and Neurosurgery Manuel Velasco Suarez, Mexico City, Mexico

    N. Monroy-Jaramillo

  4. School of Biomedical Informatics, University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA

    J. Sun

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  1. L. Stertz
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  2. V. Contreras-Shannon
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  5. C. Walss-Bass
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Correspondence to L. Stertz.

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Electronic Supplementary Material

Supplementary Figure S1

The relationship among significant networks enriched in the 91 differentially expressed genes (PNG 26 kb)

Supplementary Table 1

Differentially expressed genes (DOCX 24 kb)

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Stertz, L., Contreras-Shannon, V., Monroy-Jaramillo, N. et al. BACE1-Deficient Mice Exhibit Alterations in Immune System Pathways. Mol Neurobiol 55, 709–717 (2018). https://doi.org/10.1007/s12035-016-0341-1

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  • DOI: https://doi.org/10.1007/s12035-016-0341-1

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