Ghrelin Prevents TBI-induced Neuronal Apoptosis via Induction of Mitochondrial Uncoupling Protein 2
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Authors
Gaston, Lindsey S.
Issue Date
2012
Type
Thesis
Language
en_US
Keywords
Alternative Title
Abstract
Traumatic brain injury (TBI) is a significant cause of morbidity and mortality in
humans. Presently, no pharmacologic agent exists to prevent neuronal loss; however, the
second wave of cellular death that follows TBI occurs within a timeframe amenable to
therapeutic intervention. Previous research has demonstrated that transient mitochondrial
uncoupling may help prevent initiation of apoptosis via the intrinsic pathway. Among the
several endogenous mitochondrial uncoupling proteins identified, UCP2 has been shown
to be expressed throughout the central nervous system and to provide a protective role in
a variety of neural injury models. Moreover, production of UCP2 is upregulated when
levels of ghrelin, a protein with anti-inflammatory and anti-apoptotic properties, are
elevated. Our study sought to correlate these two observations in an experimental model
of TBI. We hypothesized that ghrelin administration would inhibit neuronal apoptosis
via induction of UCP2. BALB/c mice were divided into sham, TBI, and TBI/ghrelin
treatment groups, and TBI was induced with a weight drop model following anesthesia.
Neuronal apoptosis was characterized by staining coronal brain sections with the TUNEL
method, and relative expression levels of UCP2 and the apoptotic protein caspase-3 were
analyzed with immunohistochemistry. We found that increased UCP2 expression in
response to TBI/ghrelin treatment correlated with decreased neuronal apoptosis,
suggesting that ghrelin treatment may provide an amenable therapeutic target for
reducing neurodegeneration following TBI.
Description
iv, 41 p.
Citation
Publisher
Kalamazoo College
License
U.S. copyright laws protect this material. Commercial use or distribution of this material is not permitted without prior written permission of the copyright holder.