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Evaluating BACE-1 as a biomarker for experimental TBI in rats

Mohite, Simone (2022) Evaluating BACE-1 as a biomarker for experimental TBI in rats. Undergraduate Thesis, University of Pittsburgh. (Unpublished)

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Abstract

Moderate to Severe Traumatic Brain Injuries (TBI) are known to cause synaptic damage and increase the risk of developing neurodegenerative disorders like Alzheimer’s dementia, although there is no established technique to identify those at risk for this outcome. Beta-site amyloid precursor protein cleaving enzyme (BACE-1) has been studied as a promising serum biomarker to identify synaptic damage in Alzheimer’s disease (AD) due to its enzymatic role in Aβ 1-42 genesis, one of the hallmark proteins associated with AD. Since TBI produces synaptic damage, BACE-1 also has potential as a serum biomarker of posttraumatic synaptic damage. It is hypothesized that elevated BACE-1 levels lead to overproduction of toxic amyloid beta species, thereby increasing the risk of neurodegeneration after TBI. BACE-1 mRNA levels, BACE-1 protein levels and enzymatic activity of BACE-1 (Aβ 1-42 genesis) have previously been found to be elevated post experimental TBI in brain lysate samples. By detecting BACE-1 in serum samples, the identification of the extent of synaptic damage can be expedited, and the TBI can be treated appropriately. In this study, we investigated whether moderate TBI produced by controlled cortical impact (CCI) can cause detectable elevations in BACE-1 protein levels and whether BACE-1 has predictive value for cognitive outcomes. We used serum collected from adult, male Sprague Dawley rats via an indwelling jugular catheter at baseline, 24, 48, and 72 hours and 2 weeks after sham or CCI injury. Serum BACE-1 was measured using a commercial ELISA kit. Additionally, the rats were tested for motor and cognitive functions using Beam Balance, Beam Walking and Morris Water Maze tests. This study demonstrated novel findings that there was a significant decrease in detectable serum BACE-1 concentrations post-TBI from baseline to 72 hours, and recovery trend from 72 hours to 2 weeks. There was a significant correlation between baseline BACE-1 serum levels and performance on the Beam Balance task, suggesting that higher BACE-1 serum concentrations at baseline may be associated with worse sensorimotor functioning post injury.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Mohite, Simonesym15@pitt.edusym15
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairMeriney, Stephenmeriney@pitt.edumeriney
Committee MemberDixon, Edwardedixon@pitt.eduedixon
Committee MemberArtim, Debradea20@pitt.edudea20
Committee MemberBramblett, Helenhbramlett@med.miami.edun/a
Date: 27 April 2022
Date Type: Publication
Defense Date: 4 April 2022
Approval Date: 27 April 2022
Submission Date: 22 April 2022
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 35
Institution: University of Pittsburgh
Schools and Programs: Dietrich School of Arts and Sciences > Neuroscience
University Honors College
Degree: BPhil - Bachelor of Philosophy
Thesis Type: Undergraduate Thesis
Refereed: Yes
Uncontrolled Keywords: biomarkers; TBI; neuroscience; neurotrauma; BACE-1; neurodegeneration
Date Deposited: 27 Apr 2022 18:05
Last Modified: 27 Apr 2022 18:05
URI: http://d-scholarship.pitt.edu/id/eprint/42714

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