Reduced white matter MRI transverse relaxation rate in cognitively normal H63D-HFE human carriers and H67D-HFE mice

Mark D. Meadowcroft, Jianli Wang, Carson J. Purnell, Douglas G. Peters, Paul J. Eslinger, Elizabeth B. Neely, David J. Gill, Megha Vasavada, Fatima Ali-Rahmani, Qing X. Yang, James R. Connor

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Mutations within the HFE protein gene sequence have been associated with increased risk of developing a number of neurodegenerative disorders. To this effect, an animal model has been created which incorporates the mouse homologue to the human H63D-HFE mutation: the H67D-HFE knock-in mouse. These mice exhibit alterations in iron management proteins, have increased neuronal oxidative stress, and a disruption in cholesterol regulation. However, it remains undetermined how these differences translate to human H63D carriers in regards to white matter (WM) integrity. To this endeavor, MRI transverse relaxation rate (R2) parametrics were employed to test the hypothesis that WM alterations are present in H63D human carriers and are recapitulated in the H67D mice. H63D carriers exhibit widespread reductions in brain R2 compared to non-carriers within white matter association fibers in the brain. Similar R2 decreases within white matter tracts were observed in the H67D mouse brain. Additionally, an exacerbation of age-related R2 decrease is found in the H67D animal model in white matter regions of interest. The decrease in R2 within white matter tracts of both species is speculated to be multifaceted. The R2 changes are hypothesized to be due to alterations in axonal biochemical tissue composition. The R2 changes observed in both the human-H63D and mouse-H67D data suggest that modified white matter myelination is occurring in subjects with HFE mutations, potentially increasing vulnerability to neurodegenerative disorders.

Original languageEnglish (US)
Pages (from-to)1231-1242
Number of pages12
JournalBrain Imaging and Behavior
Volume10
Issue number4
DOIs
StatePublished - Dec 1 2016

All Science Journal Classification (ASJC) codes

  • Radiology Nuclear Medicine and imaging
  • Neurology
  • Cognitive Neuroscience
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health
  • Behavioral Neuroscience

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