| MRI and MRS alterations in the preclinical phase of murine prion disease: association with neuropathological and behavioural changes. | |
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MedLine Citation:
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PMID: 17490889 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Kerry A Broom; Daniel C Anthony; John P Lowe; Julian L Griffin; Helen Scott; Andrew M Blamire; Peter Styles; V Hugh Perry; Nicola R Sibson |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2007-04-05 |
Journal Detail:
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Title: Neurobiology of disease Volume: 26 ISSN: 0969-9961 ISO Abbreviation: Neurobiol. Dis. Publication Date: 2007 Jun |
Date Detail:
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Created Date: 2007-05-22 Completed Date: 2007-08-24 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9500169 Medline TA: Neurobiol Dis Country: United States |
Other Details:
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Languages: eng Pagination: 707-17 Citation Subset: IM |
Affiliation:
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Experimental Neuroimaging Group, Department of Physiology, Anatomy and Genetics, University of Oxford, Sherrington Building, Parks Rd., Oxford, OX1 3PT, UK. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Aspartic Acid / analogs & derivatives, analysis, metabolism Astrocytes / metabolism Body Water / physiology Brain / metabolism, pathology*, physiopathology Choline / analysis, metabolism Creatine / analysis, metabolism Diffusion Disease Models, Animal Disease Progression Gliosis / etiology, pathology, physiopathology Glucose / metabolism Glutamic Acid / analysis, metabolism Hyperkinesis / etiology, pathology, physiopathology Inositol / metabolism Magnetic Resonance Imaging / methods* Magnetic Resonance Spectroscopy / methods* Mice Mice, Inbred C57BL Microglia / metabolism Prion Diseases / diagnosis*, pathology*, physiopathology |
| Chemical | |
Reg. No./Substance:
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50-99-7/Glucose; 56-84-8/Aspartic Acid; 56-86-0/Glutamic Acid; 57-00-1/Creatine; 62-49-7/Choline; 6917-35-7/Inositol; 997-55-7/N-acetylaspartate |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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