title: BACE1-Deficient Mice Exhibit Alterations in Immune System Pathways.
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.
authors.affiliation: Translational Psychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA. Laura.Stertz@uth.tmc.edu.
authors.forename: L
authors.identifier: 0000-0002-1426-6796
authors.initials: L
authors.lastname: Stertz
authors.affiliation: Department of Biological Sciences, Saint Mary's University, San Antonio, TX, USA.
authors.forename: V
authors.initials: V
authors.lastname: Contreras-Shannon
authors.affiliation: Translational Psychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA.|Department of Genetics, National Institute of Neurology and Neurosurgery Manuel Velasco Suarez, Mexico City, Mexico.
authors.forename: N
authors.initials: N
authors.lastname: Monroy-Jaramillo
authors.affiliation: School of Biomedical Informatics, University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA.
authors.forename: J
authors.initials: J
authors.lastname: Sun
authors.affiliation: Translational Psychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA.
authors.forename: C
authors.initials: C
authors.lastname: Walss-Bass
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000172:deficiency* / Q000378:metabolism; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000172:deficiency* / Q000378:metabolism; D018925:Chemokines / Q000097:blood; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006624:Hippocampus / Q000378:metabolism; D007107:Immune System / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D038203:alpha-Crystallin B Chain / Q000235:genetics / Q000378:metabolism
chemical_list: D018925:Chemokines; C525420:Cryab protein, mouse; D012333:RNA, Messenger; D038203:alpha-Crystallin B Chain; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509282:Bace1 protein, mouse
keywords: BACE1; Hippocampus; IL-9 signaling; Immune system pathways; Schizophrenia; Transcriptome