ORCID Profile
0000-0002-0012-5968
Current Organisations
South Australian Health and Medical Research Institute Limited
,
Advance HE
,
University of Sydney
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Publisher: Wiley
Date: 15-03-2011
DOI: 10.1111/J.2042-3306.2010.00336.X
Abstract: NMR-metabonomics is an unbiased evaluation method, which allows to comprehensively study changes of the equine metabolic profile in early time point laminitis. This might give insight into the early stages of disease development. To detect hitherto unknown changes in blood metabolites during the development of oligofructose-induced laminitis by comparing pre- and post induction blood s les. Prior to laminitis induction blood was s led to establish control values. Post oligofructose administration (POA) blood was collected every 3 h for 24 h. One-dimensional (1) H-NMR spectra of the blood plasma were statistically analysed. NMR resonances of >20 metabolites were identified using this technique. Already known changes (e.g. lactate concentrations) were confirmed using this method. Interestingly, oligofructose, a carbohydrate usually considered indigestible in the small intestine, or derivatives of oligofructose, was detected in plasma. Horses also showed increased phosphatidylcholine and/or low density lipoprotein levels POA, indicating a change in blood lipid composition. An increase in phosphatidylcholine is consistent with the breakdown of the mucosal layer of the large intestine and increased permeability of the gut. Due to the nontargeted approach of metabonomics, new unexpected changes can be identified, in this case the hitherto unknown oligofructose uptake through the mucosal wall and the phospholipid changes. Metabolic changes in disease can be observed using NMR metabonomics. Oligofructose is used in feedstuffs and transport mechanisms through the mucosa should be studied. Phospholipids could point to a compromise of the intestinal wall during laminitis development.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-03-2013
Publisher: Elsevier BV
Date: 02-2013
DOI: 10.1016/J.NEUROIMAGE.2012.10.075
Abstract: Loss of basal forebrain cholinergic neurons is an early and key feature of Alzheimer's disease, and magnetic resonance imaging (MRI) volumetric measurement of the basal forebrain has recently gained attention as a potential diagnostic tool for this condition. The aim of this study was to determine whether loss of basal forebrain cholinergic neurons underpins changes which can be detected through diffusion MRI using diffusion tensor imaging (DTI) and probabilistic tractography in a mouse model. To cause selective basal forebrain cholinergic degeneration, the toxin saporin conjugated to a p75 neurotrophin receptor antibody (mu-p75-SAP) was used. This resulted in ~25% loss of the basal forebrain cholinergic neurons and significant loss of terminal cholinergic projections in the hippoc us, as determined by histology. To test whether lesion of cholinergic neurons caused basal forebrain, hippoc al, or whole brain atrophy, we performed manual segmentation analysis, which revealed no significant atrophy in lesioned animals compared to controls (Rb-IgG-SAP). However, analysis by DTI of the basal forebrain area revealed a significant increase in fractional anisotropy (FA +7.7%), mean diffusivity (MD +6.1%), axial diffusivity (AD +8.5%) and radial diffusivity (RD +4.0%) in lesioned mice compared to control animals. These parameters strongly inversely correlated with the number of choline acetyl transferase-positive neurons, with FA showing the greatest association (r(2)=0.72), followed by MD (r(2)=0.64), AD (r(2)=0.64) and RD (r(2)=0.61). Moreover, probabilistic tractography analysis of the septo-hippoc al tracts originating from the basal forebrain revealed an increase in streamline MD (+5.1%) and RD (+4.3%) in lesioned mice. This study illustrates that moderate loss of basal forebrain cholinergic neurons (representing only a minor proportion of all septo-hippoc al axons) can be detected by measuring either DTI parameters of the basal forebrain nuclei or tractography parameters of the basal forebrain tracts. These findings provide increased support for using DTI and probabilistic tractography as non-invasive tools for diagnosing and/or monitoring the progression of conditions affecting the integrity of the basal forebrain cholinergic system in humans, including Alzheimer's disease.
Publisher: No publisher found
Date: 2015
Publisher: Springer Science and Business Media LLC
Date: 26-10-2017
Abstract: Caspase-2 has been shown to be involved in metabolic homeostasis. Here, we show that caspase-2 deficiency alters basal energy metabolism by shifting the balance in fuel choice from fatty acid to carbohydrate usage. At 4 weeks of age, whole-body carbohydrate utilisation was increased in Casp2 −/− mice and was maintained into adulthood. By 17 weeks of age, Casp2 −/− mice had reduced white adipose mass, smaller white adipocytes decreased fasting blood glucose and plasma triglycerides but maintained normal insulin levels. When placed on a 12-week high-fat diet (HFD), Casp2 −/− mice resisted the development of obesity, fatty liver, hyperinsulinemia and insulin resistance. In addition, HFD-fed Casp2 −/− mice had reduced white adipocyte hypertrophy, apoptosis and expansion of both subcutaneous and visceral adipose depots. Increased expression of UCP1 and the maintenance of adiponectin levels in white adipose tissue of HFD-fed Casp2 −/− mice indicated increased browning and adipocyte hyperplasia. We found that while the preference for whole-body carbohydrate utilisation was maintained, HFD-fed Casp2 −/− mice were not impaired in their ability to switch to utilising fats as a fuel source. Our findings suggest that caspase-2 impacts basal energy metabolism by regulating adipocyte biology and fat expansion, most likely via a non-apoptotic function. Furthermore, we show that caspase-2 deficiency shifts the balance in fuel choice towards increased carbohydrate utilisation and propose that this is due to mild energy stress. As a consequence, Casp2 −/− mice show an adaptive remodelling of adipose tissue that protects from HFD-induced obesity and improves glucose homeostasis while paradoxically increasing their susceptibility to oxidative stress induced damage and premature ageing.
Publisher: Elsevier BV
Date: 09-2012
DOI: 10.1016/J.NEUROIMAGE.2012.05.061
Abstract: The C57BL mouse is the centerpiece of efforts to use gene-targeting technology to understand cerebellar pathology, thus creating a need for a detailed magnetic resonance imaging (MRI) atlas of the cerebellum of this strain. In this study we present a methodology for systematic delineation of the vermal and hemispheric lobules of the C57BL/6J mouse cerebellum in magnetic resonance images. We have successfully delineated 38 cerebellar and cerebellar-related structures. The higher signal-to-noise ratio achieved by group averaging facilitated the identification of anatomical structures. In addition, we have calculated average region volumes and created probabilistic maps for each structure. The segmentation method and the probabilistic maps we have created will provide a foundation for future studies of cerebellar disorders using transgenic mouse models.
Publisher: No publisher found
Date: 2015
Publisher: Elsevier BV
Date: 10-2011
DOI: 10.1016/J.NEUROIMAGE.2011.06.025
Abstract: The hippoc al formation plays an important role in cognition, spatial navigation, learning, and memory. High resolution magnetic resonance (MR) imaging makes it possible to study in vivo changes in the hippoc us over time and is useful for comparing hippoc al volume and structure in wild type and mutant mice. Such comparisons demand a reliable way to segment the hippoc al formation. We have developed a method for the systematic segmentation of the hippoc al formation using the perfusion-fixed C57BL/6 mouse brain for application in longitudinal and comparative studies. Our aim was to develop a guide for segmenting over 40 structures in an adult mouse brain using 30 μm isotropic resolution images acquired with a 16.4 T MR imaging system and combined using super-resolution reconstruction.
Publisher: Society of Nuclear Medicine
Date: 06-08-2015
DOI: 10.2967/JNUMED.115.159350
Abstract: We present a combined PET/7 T MR imaging and 16.4 T microscopic MR imaging dual-modality imaging approach enabling quantification of the amyloid load at high sensitivity and high resolution, and of regional cerebral blood flow (rCBF) in the brain of transgenic APP23 mice. Moreover, we demonstrate a novel, voxel-based correlative data analysis method for in-depth evaluation of amyloid PET and rCBF data. We injected 11C-Pittsburgh compound B (PIB) intravenously in transgenic and control APP23 mice and performed dynamic PET measurements. rCBF data were recorded with a flow-sensitive alternating inversion recovery approach at 7 T. Subsequently, the animals were sacrificed and their brains harvested for ex vivo microscopic MR imaging at 16.4 T with a T2*-weighted gradient-echo sequence at 30-μm spatial resolution. Additionally, correlative amyloid histology was performed. The 11C-PIB PET data were quantified to nondisplaceable binding potentials (BPND) using the Logan graphical analysis flow-sensitive alternating inversion recovery data were quantified with a simplified version of the Bloch equation. Amyloid load assessed by both 11C-PIB PET and amyloid histology was highest in the frontal cortex of transgenic mice (11C-PIB BPND: 0.93±0.08 amyloid histology: 15.1%±1.5%), followed by the temporoparietal cortex (11C-PIB BPND: 0.75±0.08 amyloid histology: 13.9%±0.7%) and the hippoc us (11C-PIB BPND: 0.71±0.09 amyloid histology: 9.2%±0.9%), and was lowest in the thalamus (11C-PIB BPND: 0.40±0.07 amyloid histology: 6.6%±0.6%). However, 11C-PIB BPND and amyloid histology linearly correlated (R2=0.82, P<0.05) and were significantly higher in transgenic animals (P<0.01). Similarly, microscopic MR imaging allowed quantifying the amyloid load, in addition to the detection of substructures within single amyloid plaques correlating with amyloid deposition density and the measurement of hippoc al atrophy. Finally, we found an inverse relationship between 11C-PIB BPND and rCBF MR imaging in the voxel-based analysis that was absent in control mice (slopetg: -0.11±0.03 slopeco: 0.004±0.005 P=0.014). Our dual-modality imaging approach using 11C-PIB PET/7 T MR imaging and 16.4 T microscopic MR imaging allowed amyloid-load quantification with high sensitivity and high resolution, the identification of substructures within single amyloid plaques, and the quantification of rCBF.
Location: Australia
Start Date: 2019
End Date: End date not available
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2019
End Date: End date not available
Funder: National Health and Medical Research Council
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