Applying Proteomics and Computational Approaches to Identify Novel Targets in Blast Associated Post-Traumatic Epilepsy
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ABSTRACT: Traumatic brain injury (TBI) remains a leading cause of post traumatic epilepsy (PTE). Blast TBI (bTBI) found in Veterans presents cognitive and behavioral disturbance such as PTE, however, the underlying mechanisms that drive the long-term sequelae are not well understood. Using an unbiased proteomics approach in a murine model of repeated bTBI (rbTBI), this study addresses this gap in knowledge. Following rbTBI, mice underwent 24/7 EEG recording for four months before collecting the cortex and hippocampus of PTE+, PTE- and sham mice. Hundreds of differentially expressed proteins were identified in the cortex and hippocampus of PTE+ and PTE- relative to sham. Focusing on protein pathways unique to PTE+ animals revealed mitochondrial function, post translational modifications, and protein transport proteins were disrupted. Computational metabolic modeling using dysregulated protein expression predicted mitochondrial proton pump dysregulation, suggesting electron transport chain dysregulation in epileptic tissue relative to PTE- and sham. Finally, data mining enabled the identification of several novel and previously validated TBI and epilepsy biomarkers in our data set, many of which were found to already be targeted by drugs in various phases of clinical testing. These findings highlight novel proteins and protein pathways that may drive the chronic PTE sequala following rbTBI.
INSTRUMENT(S): Orbitrap Fusion Lumos
ORGANISM(S): Mus Musculus (mouse)
TISSUE(S): Brain
DISEASE(S): Traumatic Brain Injury
SUBMITTER:
Keith Ray
LAB HEAD: Michelle L. Olsen
PROVIDER: PXD048228 | Pride | 2024-06-22
REPOSITORIES: Pride
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