| Animal Models of Neurodegeneration |
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Wednesday 22 April 2009 |
| Room 311 |
16:00-18:00 |
Moderators: |
Louise van der Weerd and Ruth Vreys |
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16:00 |
538. |
Young Investigator Award
Finalist:
Magnetic Resonance Imaging and
Histological Analysis of Beta-Amyloid Plaques in
Both Human Alzheimer’s Disease and APP/PS1
Transgenic Mice |
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Mark David
Meadowcroft1,2, James R. Connor3,
Michael B. Smith1, Qing X. Yang1,3
1Radiology, Pennsylvania State University -
College of Medicine, Hershey, PA, USA; 2Neural
and Behavioral Sciences, Pennsylvania State
University - College of Medicine, Hershey, PA, USA;
3Neurosurgery, Pennsylvania State
University - College of Medicine, Hershey, PA, USA |
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The histo-pathological
basis of image contrast associated with Aβ plaques
and the connected relaxation mechanism has not been
well-understood. T2*-weighted images and
R2* parametric maps were compared to
histology stains from the same set of AD and APP/PS1
tissue slices. The electronic microscopy and
histology images revealed differences in plaque
morphology and associated iron concentration between
APP/PS1 mice and AD tissue. T2* contrast
of Aβ-plaques was associated with the gradation of
iron concentration and plaque morphology. These data
suggested a duality in the relaxation mechanism
where both focal iron concentration and highly
compact fibrillar Aβ masses cause rapid proton
transverse magnetization decay. |
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16:20 |
539. |
Imaging Biophysics of Axonal
Transport with MEMRI: Optic Tract Transport Is
Altered in Mouse Model of Alzheimer's Disease |
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Elaine L. Bearer1,
Xiaowei Zhang2, Octavian Biris1,
Russell E. Jacobs2
1Pathology and Laboratory Medicine, Brown
University, Providence, RI, USA; 2Biology,
California Institute of Technology, Pasadena, CA,
USA |
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Alterations in transport
dynamics are implicated in neurodegenerative
diseases. We are using MEMRI to image the biophysics
of intra-neuronal axonal transport and correlate
rates of MR intensity changes with genetic/molecular
differences in transport mechanics. Here we compare
Mn++ transport dynamics observed by capturing 6-min
time-lapse MR images in the polarized neural
processes of the optic track between aged mice
expressing an APP mutant correlated with Alzheimer'
disease in humans (swAPP) and their wild-type
age-matched counterparts. Our findings show that
transport dynamics in the optic track are altered in
the swAPP mouse, an Alzheimer's disease model. |
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16:32 |
540. |
Early Impaired Axonal
Transport in a Triple Transgenic Mouse Model of
Alzheimer’s Disease |
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Jieun Kim1,
In-Young Choi1,2, Mary L. Michaelis3,
Sang-Pil Lee1,4
1Hoglund Brain Imaging Center, University of
Kansas Medical Center, Kansas City, KS, USA; 2Department
of Neurology, Molecular & Integrative Physiology,
University of Kansas Medical Center, Kansas City,
KS, USA; 3Department of Pharmacology and
Toxocology, University of Kansas, Lawrence, KS, USA;
4Department of Molecular & Integrative
Physiology, University of Kansas Medical Center,
Kansas City, KS, USA |
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Axonal transport deficit
has been implicated as a common mechanism of
Alzheimer’s disease (AD) pathology. We used MEMRI to
measure fast axonal transport rates in olfactory
bulbs and olfactory cortex of a triple transgenic
mouse model of AD (3xTg). Our results indicate that
axonal transport deficit starts as early as 3 months
of age and precedes Aβ plaque and neuro-fibrillary
tangle pathology. |
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16:44 |
541. |
Longitudinal Assessment of
Neurodegeneration in a Spinocerebellar Ataxia Type 1
(SCA1) Mouse Model by 1H MRS at 9.4
Tesla: Correlation with Histopathology |
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Gulin Oz1,
H. Brent Clark1, Christopher D. Nelson1,
Dee M. Koski1, Pierre-Gilles Henry1,
Malgorzata Marjanska1, Dinesh K.
Deelchand1, Harry T. Orr1
1University of Minnesota, Minneapolis, MN, USA |
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To assess the
sensitivity of high field 1H MRS to
disease onset and progression in neurodegenerative
diseases, we measured cerebellar neurochemical
profiles of a mouse model of spinocerebellar ataxia
1 (SCA1) and controls at 3 different ages at 9.4T
using short-echo LASER. Multiple biomarkers clearly
distinguished the mutant animals from controls at
all ages. Multiple MRS measures were significantly
different in the mutant animals already at 6 weeks,
prior to significant pathological and neurological
changes. These data demonstrate the ability of MRS
to non-invasively detect pre-clinical disease, as
well as its sensitivity to disease progression. |
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16:56 |
542. |
Assessment of
Neurodegeneration Reversal in a Spinocerebellar
Ataxia Type 1 (SCA1) Mouse Model by 1H
MRS at 9.4 Tesla |
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Gulin Oz1,
H. Brent Clark1, Christopher D. Nelson1,
Dee M. Koski1, Manda L. Vollmers1,
Harry T. Orr1
1University of Minnesota, Minneapolis, MN, USA |
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To assess the
sensitivity of high field 1H MRS to
reversal of neurodegeneration, we utilized a
conditional mouse model of SCA1. We turned off the
mutated gene from 12-24 weeks and measured
cerebellar neurochemical profiles of treated and
untreated conditional mice and controls at 9.4T
using short echo LASER and LCModel. The altered
levels of multiple biomarkers partially reversed to
control values at 24 weeks in the treated mice, in
agreement with partial reversal of Purkinje cell
pathology. These data demonstrate the ability of MRS
to non-invasively detect disease reversal and its
potential utility in future pre-clinical and
clinical trials. |
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17:08 |
543. |
Increased VEGF Expression
Correlates with Severely Reduced Cerebral Perfusion
in Glutaric Acidemia Type I (GA-1) Mouse Model of
Diet Induced Encephalopathy |
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Jelena Lazovic1,
William J. Zinnanti1,2, Ellen Wolpert3,
David A. Antonetti3, Russell E. Jacobs1
1Biology, California Institute of Technology,
Pasadena, CA, USA; 2Biochemistry,
Pennsylvania State University, Hershey, PA, USA;
3Physiology, Pennsylvania State
University, Hershey, PA, USA |
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The neuroprotective role
of vascular endothelial factor (VEGF) following
cerebral ischemia remains highly controversial. The
inborn error of metabolism glutaric acidemia type-1
(GA-1) is frequently associated with cerebral and
retinal hemorrhages, and affected individuals often
experience ischemic injury involving basal ganglia.
To investigate the relationship between VEGF
expression and ischemic injury we measured cerebral
blood flow using arterial spin labeling method, and
VEGF protein levels in mouse model of GA-1.
Significantly increased levels of VEGF correlated
with severely reduced perfusion, and were found in
encephalopathic mice. |
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17:20 |
544. |
Deformation-Based Morphometry
in the R6/2 Huntington's Disease Mouse Brain |
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Stephen J. Sawiak1,
Nigel I. Wood2, G B. Williams1,
A J. Morton3, T A. Carpenter1
1Wolfson Brain Imaging Centre, University of
Cambridge, Cambridge, UK; 2Department of
Pharmacology, University of Cambridge; 3Department
of Pharmacology, University of Cambridge, UK |
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With the relative ease
of creating transgenic mouse models of disease, mice
are increasingly used for studying pathology.
Automated analysis techniques are of increasing
importance to deal with overwhelming amounts of
data. Having previously examined the phenotype of
the R6/2 Huntington's model with voxel-based
morphometry (VBM) here we present our findings with
an increased dataset of 116 images, using
deformation-based morphometry (DBM), showing it to
be more sensitive in finding differences within the
same tissue classes. |
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17:32 |
545. |
Tract Based Spatial Statistics
in Mouse Model of Neurodegerative
Unverricht-Lundborg (EPM1) Disease |
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Otto Heikki Henrikki
Manninen1, Kimmo K. Lehtimäki2,
Teemu Laitinen3, Tarja Joensuu1,
Outi Kopra1, Anna-Elina Lehesjoki1,
Olli Gröhn3
1Folkhälsan Inst. of Genetics and Neuroscience
Center, University of Helsinki, Helsinki, Finland;
2Department of Biotechnology and
Molecular Medicine, University of Kuopio, Kuopio,
Finland; 3Dept. of Neurobiology,
A.I.Virtanen Institute for Molecular Sciences,
University of Kuopio, Kuopio, Finland |
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We implemented a
recently introduced whole brain voxelwise
statistical analysis method, tract based spatial
statistics (TBSS), into a mouse model of
neurodegenerative disease, introducing TBSS in mice.
Doing black box statistical comparison of diffusion
tensor imaging (DTI) parameters between controls and
affected animals, TBSS revealed areas of
significantly redused FA compared to controls in
both brain regions known to be associated with mouse
model of Unverricht-Lundborg disease as well as
regions not earlier connected with the disease,
promising great potential to serve as a robust
screening method to guide histological analysis to
novel target areas in the brain. |
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17:44 |
546. |
In Vivo Brain
Phenotypes of the Reeler Mutant Mouse by Using
DT-MRI and MEMRI |
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Laura-Adela Harsan1,
Csaba David2, Dominik Paul1,
Susanne Schnell1, Jürgen Hennig1,
Jochen F. Staiger2, Dominik von
Elverfeldt1
1Diagnostic Radiology, Medical Physics,
University Hospital, Freiburg, Germany; 2Department
of Neuroanatomy, Institute for Anatomy and Cell
Biology, Center for Neuroscience, Freiburg, Germany |
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In the present study,
the brain cytoarchitecture of the Reeler mutant
mouse was visualized by using MEMRI while the neural
connectivity was depicted in-vivo and
non-invasively by DT-MRI. Disorganization of the
neuronal layers was clearly visible in cortical
structures of the Reeler brain. In-vivo
DT-MRI and fiber tracking showed distorted axonal
pathways when compared to wild type brain.
Particularly, Reeler mice have poorly compacted
thalamic axonal bundles that project abnormally into
the cortical structures. Furthermore, color-coded
maps evidenced abnormalities at the level of the
cingulum structure in Reeler mice and depicted the
failure in the cerebellar cortex lamination. |
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