In vivo detection of metabolic changes in a mouse model of scrapie using nuclear magnetic resonance spectroscopy

Bell, Jimmy D.; Cox, I. Jane; Williams, Steven; Belton, P. S.; McConnell, I.; Hope, James

doi:10.1099/0022-1317-72-10-2419

Cited by 15 publications

(13 citation statements)

References 29 publications

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“…Reduced levels of NAA have been reported in many other situations including Huntington's disease42, HIV43, 44, stroke45–47, the myodystrophic mouse48, 49, the mouse model for scrapie50, Alzheimer's51, Parkinson's52, drug use53 and malignant brain tumors54. Increased level of NAA in the brain is specific for CD.…”

Section: Discussionmentioning

confidence: 99%

Knock-out mouse for Canavan disease: a model for gene transfer to the central nervous system

et al. 2000

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Section: Discussionmentioning

confidence: 99%

Knock-out mouse for Canavan disease: a model for gene transfer to the central nervous system

et al. 2000

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“…All these previous studies were done at low magnetic field and only a few metabolites were measured (i.e. NAA, tCr, tCho, and sometimes Ins) and mainly metabolite ratios were reported and not absolute concentrations [7][8][9][10][11][12][13][14]. These studies reported changes in Ins and NAA concentrations.…”

Section: Discussionmentioning

confidence: 87%

“…This number is even smaller for animal models [12][13][14]. In addition, only a few metabolites were reported in these studies (mainly NAA).…”

Section: Introductionmentioning

confidence: 97%

In Vivo Longitudinal 1H MRS Study of Transgenic Mouse Models of Prion Disease in the Hippocampus and Cerebellum at 14.1 T

et al. 2015

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In vivo 1 H MR spectroscopy allows the non invasive characterization of brain metabolites and it has been used for studying brain metabolic changes in a wide range of neurodegenerative diseases. The prion diseases form a group of fatal neurodegenerative diseases, also described as transmissible spongiform encephalopathies. The mechanism by which prions elicit brain damage remains unclear and therefore different transgenic mouse models of prion disease were created. We performed an in vivo longitudinal 1 H MR spectroscopy study at 14.1 T with the aim to measure the neurochemical profile of Prnp -/-and PrP D32-121 mice in the hippocampus and cerebellum. Using high-field MR spectroscopy we were able to analyze in details the in vivo brain metabolites in Prnp -/-and PrP D32-121 mice. An increase of myo-inositol, glutamate and lactate concentrations with a decrease of N-acetylaspartate concentrations were observed providing additional information to the previous measurements.Keywords In vivo proton magnetic resonance spectroscopy Á Brain metabolites Á Mouse brain Á Prion disease

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“…The TSE's are primarily a disease of the nervous system and there is much published evidence of temporal pathological events where one would expect changes in protein expression, for example, in the murine model described in this study, changes in the synapses and in the dendrites are present at an early stage of disease [18,23,24]. Protein expression differences identified using the SELDI-TOF technology, although not definitive, may be indicative of these pathological changes.…”

Section: Discussionmentioning

confidence: 99%

Differential protein profiling as a potential multi-marker approach for TSE diagnosis

et al. 2009

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BackgroundTransmissible spongiform encephalopathy describes a family of diseases affecting both man and animals. Current tests for the diagnosis of these diseases are based on the detection of an abnormal misfolded form of the host protein PrP which is found within the central nervous and lymphoreticular systems of affected animals. Recently, concern that this marker may not be as reliable as previously thought, coupled with an urgentneed for a pre-clinical live animal test, has led to the search for alternative assays for the detection of TSE disease.MethodsThis "proof of concept" study, examines the use of differential protein expression profiling using surface enhanced laser desorption and ionisationtime of flight mass spectrometry (SELDI-TOF) for the diagnosis of TSE disease. Spectral output from all proteins selectively captured from individual murine brain homogenate samples, are compared as "profiles" in groups of infected and non-infected animals. Differential protein expression between groups is thus highlighted and statistically significant protein "peaks" used to construct a panel of disease specific markers.Studies at both terminal stages of disease and throughout the time course of disease have shown a disease specific protein profile or "disease fingerprint" which could be used to distinguish between groups of TSE infected and uninfected animals at an early time point of disease.ResultsOur results show many differentially expressed proteins in diseased and control animals, some at early stages of disease. Three proteins identified by SELDI-TOF analysis were verified by immunohistochemistry in brain tissue sections. We demonstrate that by combining the most statistically significant changes in expression, a panel of markers can be constructed that can distinguish between TSE diseased and normal animals.ConclusionDifferential protein expression profiling has the potential to be used for the detection of disease in TSE infected animals. Having established that a "training set" of potential markers can be constructed, more work would be required to further test the specificity and sensitivity of the assay in a "testing set". Based on these promising results, further studies are being performed using blood samples from infected sheep to assess the potential use of SELDI-TOF as a pre-mortem blood based diagnostic.

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In vivo detection of metabolic changes in a mouse model of scrapie using nuclear magnetic resonance spectroscopy

Cited by 15 publications

References 29 publications

Knock-out mouse for Canavan disease: a model for gene transfer to the central nervous system

Knock-out mouse for Canavan disease: a model for gene transfer to the central nervous system

In Vivo Longitudinal 1H MRS Study of Transgenic Mouse Models of Prion Disease in the Hippocampus and Cerebellum at 14.1 T

Differential protein profiling as a potential multi-marker approach for TSE diagnosis

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