MRI and MRS alterations in the preclinical phase of murine prion disease: Association with neuropathological and behavioural changes
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 w...
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| Format: | Article |
| Language: | English |
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Elsevier
2007-06-01
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| Series: | Neurobiology of Disease |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996107000794 |
| _version_ | 1818616192877723648 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Kerry A. Broom |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-16T16:45:54Z |
| format | Article |
| id | doaj.art-64e0f0851a2945a8b00da552e3f130a5 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-16T16:45:54Z |
| publishDate | 2007-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-64e0f0851a2945a8b00da552e3f130a52022-12-21T22:24:11ZengElsevierNeurobiology of Disease1095-953X2007-06-01263707717MRI and MRS alterations in the preclinical phase of murine prion disease: Association with neuropathological and behavioural changesKerry A. Broom0Daniel C. Anthony1John P. Lowe2Julian L. Griffin3Helen Scott4Andrew M. Blamire5Peter Styles6V. Hugh Perry7Nicola R. Sibson8Experimental Neuroimaging Group, Department of Physiology, Anatomy and Genetics, University of Oxford, Sherrington Building, Parks Rd., Oxford, OX1 3PT, UKMolecular Neuropathology Group, Department of Pharmacology, University of Oxford, UKDepartment of Chemistry, University of Bath, UKDepartment of Biochemistry, University of Cambridge, UKCNS Inflammation Group, School of Biological Sciences, University of Southampton, UKSchool of Clinical and Laboratory Sciences, University of Newcastle upon Tyne, UKExperimental Neuroimaging Group, Department of Physiology, Anatomy and Genetics, University of Oxford, Sherrington Building, Parks Rd., Oxford, OX1 3PT, UKCNS Inflammation Group, School of Biological Sciences, University of Southampton, UKExperimental Neuroimaging Group, Department of Physiology, Anatomy and Genetics, University of Oxford, Sherrington Building, Parks Rd., Oxford, OX1 3PT, UK; Corresponding author. Fax: +44 1865 272515.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.http://www.sciencedirect.com/science/article/pii/S0969996107000794Magnetic resonanceDiffusionN-acetyl aspartatePrionChronic inflammationBrain |
| spellingShingle | 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 MRI and MRS alterations in the preclinical phase of murine prion disease: Association with neuropathological and behavioural changes Neurobiology of Disease Magnetic resonance Diffusion N-acetyl aspartate Prion Chronic inflammation Brain |
| title | MRI and MRS alterations in the preclinical phase of murine prion disease: Association with neuropathological and behavioural changes |
| title_full | MRI and MRS alterations in the preclinical phase of murine prion disease: Association with neuropathological and behavioural changes |
| title_fullStr | MRI and MRS alterations in the preclinical phase of murine prion disease: Association with neuropathological and behavioural changes |
| title_full_unstemmed | MRI and MRS alterations in the preclinical phase of murine prion disease: Association with neuropathological and behavioural changes |
| title_short | MRI and MRS alterations in the preclinical phase of murine prion disease: Association with neuropathological and behavioural changes |
| title_sort | mri and mrs alterations in the preclinical phase of murine prion disease association with neuropathological and behavioural changes |
| topic | Magnetic resonance Diffusion N-acetyl aspartate Prion Chronic inflammation Brain |
| url | http://www.sciencedirect.com/science/article/pii/S0969996107000794 |
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