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Please use this identifier to cite or link to this item: http://arks.princeton.edu/ark:/88435/dsp017h149s502
Title: The Impact of an Impact: Telomere Length and Telomerase Activity in Cells of the Central Nervous System Following Moderate Controlled Cortical Impact Injuries in Mice
Contributors: Notterman, Daniel A.
Katchur, Nicole
Issue Date: 13-Jun-2017
Abstract: Traumatic brain injury (TBI) affects over 57 million people globally each year, of whom 1.4 million live in the United States. There are 475,000 new cases of pediatric traumatic brain injury per year, accounting for 3,000 to 4,000 deaths. Traumatic brain injury (TBI) differs from ischemic stroke and other non-mechanical injuries in that head trauma exposes cells of the central nervous system (CNS) to shear force, tensile stress, and compression forces. In addition to physical disruption of neural structures, these forces induce damaging activation of cellular stress and inflammation pathways. The resulting cellular processes following a traumatic brain injury may damage DNA, including the telomeres. Telomeres are the end chromosomal structures comprised of tandem repeating base pairs (of nucleotide sequence TTAGGG) that protect genetic information. Due to the end replication problem, in the absence of telomeres, the chromosomal ends shorten as DNA replicates. The presence of the telomere buffers this effect. In some cell lineages, telomerase maintains telomere length during replication. In most somatic cells, however, telomere attrition occurs naturally due to aging, oxidative stress, and other mechanisms. Further, telomerase activity is implicated in neurogenesis and may affect how neural and glial cells survive. Cells with active telomerase are more resistant to cellular apoptosis. Recent literature suggests that telomere attrition may be accelerated by TBI and TBI may induce telomerase activity. Previous studies show that telomerase activity was induced in mice hippocampi following kainate-induced seizures and telomere lengths shortened in some rats as a result of a mild concussive TBI, but experimental conditions did not permit a definitive statement as to the link between the level of trauma and telomere length. It is not clear how a moderate traumatic brain injury affects telomerase activity and telomere lengths. To address this gap, we sought to measure telomerase activity and telomere lengths in cells of the CNS both 24 hours and 14 days following a moderate Controlled Cortical Impact (CCI) injury in adult male mice. We found changes in telomerase activity in the ipsilateral cortex, thalamus, and hippocampus 24 hours following injury, and telomerase activity remained present in these regions 14 days following injury. Telomerase activity in some tissues were statistically significant when compared to controls. Additionally, we found significant telomere length changes in the cells of the CNS 14 days following TBI. Telomere elongation occurred in the ipsilateral cortex, telomere maintenance occurred in the ipsilateral hippocampus, and telomere attrition occurred in the ipsilateral thalamus. Correlation between a moderate traumatic brain injury and telomere length mediated by telomerase activity 1 day after a moderate CCI injury may suggest a possible molecular mechanism by which telomeres change after a traumatic brain injury, providing insight for possible future medical treatment and intervention. Future studies should investigate the types of cells expressing telomerase and changes in telomere lengths to better understand the implications that telomere length and telomerase activity have in neurogenesis and to elucidate the cellular mechanism by which telomere changes occur following a traumatic brain injury.
URI: http://arks.princeton.edu/ark:/88435/dsp017h149s502
Appears in Collections:Neuroscience, 2017

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