Does TBI Affect mtDNA Heteroplasmy?
Abstract
This collaborative project sought to better understand the long-term consequences of traumatic brain injury (TBI) as theypertain to Alzheimers disease (AD). To accomplish this, we conducted a series of experiments to explore connectionsbetween TBI, brain aging, and mitochondrial DNA (mtDNA) mutations. Our central hypothesis was that TBI accelerates theage-related accumulation of mtDNA microheteroplasmic mutations, and that this can explain the recognized associationbetween TBI and AD. To test this, we exposed young adult mice to a TBI or sham injury and let the mice age.Age-related tissue shrinkage made the quantification of ultra-low frequency heteroplasmic mutations in mouse hippocampussamples too unreliable, so we pursued an alternate approach by quantifying mitochondrial DNA copy number (mtDNAcn),another marker of aging-related mitochondrial change. We found an enhanced aging-related mtDNAcn increase in braininjured mice compared to controls, suggesting that the amount of compensation required to preserve mitochondrial functionlate in life may be greater after a brain injury. TBI may, therefore, increase AD risk by affecting the biology or trajectory ofaging-related mitochondrial adaptation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2022
- Accession Number
- AD1215432
Entities
People
- Janna Harris
Organizations
- University of Kansas Medical Center