Anatomical and functional phenotyping of mice models of Alzheimer's disease by MR microscopy

被引:28
作者
Benveniste, Helene
Ma, Yu
Dhawan, Jasbeer
Gifford, Andrew
Smith, S. David
Feinstein, Igor
Du, Congwu
Grant, Samuel C.
Hof, Patrick R.
机构
[1] Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA
[2] SUNY Stony Brook, Dept Anesthesiol, New York, NY USA
[3] Florida State Univ, Dept Chem & Biomed Engn, Tallahassee, FL 32306 USA
[4] Natl High Magnet Field Lab, Tallahassee, FL USA
[5] Mt Sinai Sch Med, Dept Neurosci, New York, NY USA
来源
IMAGING AND THE AGING BRAIN | 2007年 / 1097卷
关键词
MR microscopy; phenotyping; imaging; mice; Alzheimer's disease; model; MAGNETIC-RESONANCE MICROSCOPY; DIRECT THALAMIC-STIMULATION; AMYLOID PRECURSOR PROTEIN; CORPUS-CALLOSUM ATROPHY; TRIPLE-TRANSGENIC MODEL; INTRACELLULAR A-BETA; MOUSE MODEL; HUMAN BRAIN; RELAXATION-TIMES; HYPOXIA-ISCHEMIA;
D O I
10.1196/annals.1379.006
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The wide variety of transgenic mouse models of Alzheimer's disease (AD) reflects the search for specific genes that influence AD pathology and the drive to create a clinically relevant animal model. An ideal AD mouse model must display hallmark AD pathology such as amyloid plaques, neurofibrillary tangles, reactive gliosis, dystrophic neurites, neuron and synapse loss, and brain atrophy and in parallel behaviorally mimic the cognitive decline observed in humans. Magnetic resonance (MR) microscopy (MRM) can detect amyloid plaque load, development of brain atrophy, and acute neurodegeneration. MRM examples of AD pathology will be presented and discussed. What has lagged behind in preclinical research using transgenic AD mouse models is functional phenotyping of the brain; in other words, the ability to correlate a specific genotype with potential aberrant brain activation patterns. This lack of information is caused by the technical challenges involved in performing functional MRI (fMRI) in mice including the effects of anesthetic agents and the lack of relevant '' cognitive '' paradigms. An alternative approach to classical fMRI using external stimuli as triggers of brain activation in rodents is to electrically or pharmacologically stimulate regions directly while simultaneously locally tracking the activated interconnected regions of rodents using, for example, the manganese-enhanced MRI (MEMRI) technique. Finally, transgenic mouse models, MRM, and future AD research would be strengthened by the ability to screen for AD-like pathology in other non-AD transgenic mouse models. For example, molecular biologists may focus on cardiac or pulmonary pathologies in transgenic mice models and as an incidental finding discover behavioral AD phenotypes. We will present MRM data of brain and cardiac phenotyping in transgenic mouse models with behavioral deficits.
引用
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页码:12 / 29
页数:18
相关论文
共 79 条
[1]   Confounding effects of anesthesia on functional activation in rodent brain:: a study of halothane and α-chloralose anesthesia [J].
Austin, VC ;
Blamire, AM ;
Allers, KA ;
Sharp, T ;
Styles, P ;
Matthews, PM ;
Sibson, NR .
NEUROIMAGE, 2005, 24 (01) :92-100
[2]   The dopamine D4 receptor is essential for hyperactivity and impaired behavioral inhibition in a mouse model of attention deficit/hyperactivity disorder [J].
Avale, ME ;
Falzone, TL ;
Gelman, DM ;
Low, MJ ;
Grandy, DK ;
Rubinstein, M .
MOLECULAR PSYCHIATRY, 2004, 9 (07) :718-726
[3]   Responses of neurons in primary and inferior temporal visual cortices to natural scenes [J].
Baddeley, R ;
Abbott, LF ;
Booth, MCA ;
Sengpiel, F ;
Freeman, T ;
Wakeman, EA ;
Rolls, ET .
PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, 1997, 264 (1389) :1775-1783
[4]   MR microscopy and high resolution'small animal MRI: applications in neuroscience research [J].
Benveniste, H ;
Blackband, S .
PROGRESS IN NEUROBIOLOGY, 2002, 67 (05) :393-420
[5]   Detection of neuritic plaques in Alzheimer's disease by magnetic resonance microscopy [J].
Benveniste, H ;
Einstein, G ;
Kim, KR ;
Hulette, C ;
Johnson, A .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (24) :14079-14084
[6]   Translational neuroscience and magnetic-resonance microscopy [J].
Benveniste, Helene ;
Blackband, Stephen J. .
LANCET NEUROLOGY, 2006, 5 (06) :536-544
[7]   In vivo magnetic resonance imaging and semiautomated image analysis extend the brain phenotype for cdf/cdf mice [J].
Bock, NA ;
Kovacevic, N ;
Lipina, TV ;
Roder, JC ;
Ackerman, SL ;
Henkelman, RM .
JOURNAL OF NEUROSCIENCE, 2006, 26 (17) :4455-4459
[8]   Linear systems analysis of functional magnetic resonance imaging in human V1 [J].
Boynton, GM ;
Engel, SA ;
Glover, GH ;
Heeger, DJ .
JOURNAL OF NEUROSCIENCE, 1996, 16 (13) :4207-4221
[9]   NEUROPATHOLOGICAL STAGING OF ALZHEIMER-RELATED CHANGES [J].
BRAAK, H ;
BRAAK, E .
ACTA NEUROPATHOLOGICA, 1991, 82 (04) :239-259
[10]  
CHANCE B, 1993, ADV EXP MED BIOL, V333, P1