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Lookup NU author(s): Professor Andrew BlamireORCiD
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Prion diseases are fatal chronic neurodegenerative diseases. Previous qualitative magnetic resonance imaging (MRI) and spectroscopy (MRS) studies report conflicting results in the symptomatic stages of the disease, but little work has been carried out during the earlier stages of the disease. Here we have used the murine ME7 model of prion disease to quantitatively investigate MRI and MRS changes during the period prior to the onset of overt clinical signs (20+ weeks) and have correlated these with pathological and behavioural abnormalities. Using in vivo MRI, at the later stages of the preclinical period (18 weeks) the diffusion of tissue water was significantly reduced, coinciding with significant microglial activation and behavioural hyperactivity. Using in vivo MRS, we found early (12 weeks) decreases in the ratio of N-acetyl aspartate to both choline (NAA/Cho) and creatine (NAA/Cr) in the thalamus and hippocampus, which were associated with early behavioural deficits. Ex vivo MRS of brain extracts confirmed and extended these findings, showing early (8-12 weeks) decreases in both the neuronal metabolites NAA and glutamate, and the metabolic metabolites lactate and glucose. Increases in the glial metabolite myo-inositol were observed at later stages when microglial and astrocyte activation is substantial. These changes in MRI and MRS signals, which precede overt clinical signs of disease, could provide insights into the pathogenesis of this disease and may enable early detection of pathology. © 2007 Elsevier Inc. All rights reserved.
Author(s): Broom KA, Anthony DC, Lowe JP, Griffin JL, Scott H, Blamire AM, Styles P, Hugh Perry V, Sibson NR
Publication type: Article
Publication status: Published
Journal: Neurobiology of Disease
Year: 2007
Volume: 26
Issue: 3
Pages: 707-717
ISSN (print): 0969-9961
ISSN (electronic): 1095-953X
Publisher: Academic Press
URL: http://dx.doi.org/10.1016/j.nbd.2007.04.001
DOI: 10.1016/j.nbd.2007.04.001
PubMed id: 17490889
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