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Published, Version of Record (VoR)Open Access (License Unspecified), Open
Journal article
Strong Correlation of Genome-Wide Expression after Traumatic Brain Injury In Vitro and In Vivo Implicates a Role for SORLA
Journal of neurotrauma, v 34(1)
01 Jan 2017
PMID: 26919808
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The utility of
in vitro
models of traumatic brain injury (TBI) depends on their ability to recapitulate the
in vivo
TBI cascade. In this study, we used a genome-wide approach to compare changes in gene expression at several time points post-injury in both an
in vitro
model and an
in vivo
model of TBI. We found a total of 2073 differentially expressed genes in our
in vitro
model and 877 differentially expressed genes in our
in vivo
model when compared to noninjured controls. We found a strong correlation in gene expression changes between the two models (
r
= 0.69), providing confidence that the
in vitro
model represented at least part of the
in vivo
injury cascade. From these data, we searched for genes with significant changes in expression over time (analysis of covariance) and identified sorting protein-related receptor with A-type repeats (SORLA). SORLA directs amyloid precursor protein to the recycling pathway by direct binding and away from amyloid-beta producing enzymes. Mutations of SORLA have been linked to Alzheimer's disease (AD). We confirmed downregulation of SORLA expression in organotypic hippocampal slice cultures by immunohistochemistry and Western blotting and present preliminary data from human tissue that is consistent with these experimental results. Together, these data suggest that the
in vitro
model of TBI used in this study strongly recapitulates the
in vivo
TBI pathobiology and is well suited for future mechanistic or therapeutic studies. The data also suggest the possible involvement of SORLA in the post-traumatic cascade linking TBI to AD.
Metrics
Details
- Title
- Strong Correlation of Genome-Wide Expression after Traumatic Brain Injury In Vitro and In Vivo Implicates a Role for SORLA
- Creators
- Michael R. Lamprecht - Columbia UniversityBenjamin S. Elkin - Columbia UniversityKartik Kesavabhotla - Columbia UniversityJohn F. Crary - Allen Institute for Brain ScienceJennifer L. Hammers - Office of Chief Medical ExaminerJimmy W. Huh - Children's Hospital of PhiladelphiaRamesh Raghupathi - Drexel UniversityBarclay Morrison - Columbia University
- Publication Details
- Journal of neurotrauma, v 34(1)
- Publisher
- Mary Ann Liebert, Inc
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000390420100012
- Scopus ID
- 2-s2.0-85008235153
- Other Identifier
- 991019167745604721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Clinical Neurology
- Critical Care Medicine
- Neurosciences