Longitudinal neuroanatomical changes determined by deformation-based morphometry in a mouse model of Alzheimer's disease

Lau, Jonathan C.; Lerch, Jason P.; Sled, John G.; Henkelman, R. Mark; Evans, Alan C.; Bedell, Barry J.

doi:10.1016/j.neuroimage.2008.04.252

Cited by 136 publications

(123 citation statements)

References 51 publications

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“…That optimization and the smaller voxels needed for the mouse brain required 12-24 h scan times, which raised the practical need to image multiple mice in the same scan [107,127]. Furthermore, improved image analysis techniques [94,108,111,128] and mouse atlases [129] were created to aid in the neuroanatomical analysis of the mouse. All of these improvements allowed dramatic advances in the neuroanatomical assessments in mouse model of human disease.…”

Section: Initial Investigations With Mri (1994-2010)mentioning

confidence: 99%

“…This method allowed a greater specificity in order to determine subtle changes that may or may not have been seen in the previous in vivo examinations. In 2010, the Fmr1 KO mouse was revisited on a C57BL/6 J background using highresolution MRI [130], which reported volumes for 62 different brains regions [129], encompassing the whole brain, as well as voxel-wise differences that highlight local differences found within those regions [128]. Similar to the initial Fmr1 examination by Kooy et al [115], no differences were found in total brain volume.…”

Section: Recent Investigations (2010-14)mentioning

confidence: 99%

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Behavioral and Neuroanatomical Phenotypes in Mouse Models of Autism

2015

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In order to understand the consequences of the mutation on behavioral and biological phenotypes relevant to autism, mutations in many of the risk genes for autism spectrum disorder have been experimentally generated in mice. Here, we summarize behavioral outcomes and neuroanatomical abnormalities, with a focus on highresolution magnetic resonance imaging of postmortem mouse brains. Results are described from multiple mouse models of autism spectrum disorder and comorbid syndromes, including the 15q11-13, 16p11.2, 22q11.2, Cntnap2, Engrailed2, Fragile X, Integrinβ3, MET, Neurexin1a, Neuroligin3, Reelin, Rett, Shank3, Slc6a4, tuberous sclerosis, and Williams syndrome models, and inbred strains with strong autism-relevant behavioral phenotypes, including BTBR and BALB. Concomitant behavioral and neuroanatomical abnormalities can strengthen the interpretation of results from a mouse model, and may elevate the usefulness of the model system for therapeutic discovery.

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Section: Initial Investigations With Mri (1994-2010)mentioning

confidence: 99%

Section: Recent Investigations (2010-14)mentioning

confidence: 99%

Behavioral and Neuroanatomical Phenotypes in Mouse Models of Autism

2015

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“…Magnetic resonance images were acquired with a 7-T Bruker Pharmascan system (Bruker Biospin, Ettlingen, Germany) using a 28-mm inner-diameter quadrature volume resonator, and a three-dimensional TrueFISP (True fast imaging with steady-state precession) sequence with the following parameters: matrix size = 128 Â 128 Â 64, field of view = 1.8 Â 1.8 Â 0.9 cm 3 , spatial resolution = 140 Â 140 Â 140 mm 3 , excitation flip angle = 301, repetition time = 5.2 milliseconds, echo time = 2.6 milliseconds, number of excitations (NEX) = 4, number of phase cycles = 4, and total scan time = 35 minutes. The images were reconstructed using a maximum intensity algorithm, and the population averages were generated using the approach described by Lau et al (2008). Evoked CGU was expressed as a SUV ratio of the maximally activated somatosensory cortex (contralateral to whisker stimulation) to the analogous area of the ipsilateral cortex.…”

Section: -Deoxy-2-[ 18 F]fluoro-d-glucose-positron-emission Tomographymentioning

confidence: 99%

Intact Memory in TGF-β1 Transgenic Mice Featuring Chronic Cerebrovascular Deficit: Recovery with Pioglitazone

Nicolakakis

Aboulkassim

Aliaga

et al. 2010

J Cereb Blood Flow Metab

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The roles of chronic brain hypoperfusion and transforming growth factor-beta 1 (TGF-b1) in Alzheimer's disease (AD) are unresolved. We investigated the interplay between TGF-b1, cerebrovascular function, and cognition using transgenic TGF mice featuring astrocytic TGF-b1 overexpression. We further assessed the impact of short, late therapy in elderly animals with the antioxidant N-acetyl-L-cysteine (NAC) or the peroxisome proliferator-activated receptor-c agonist pioglitazone. The latter was also administered to pups as a prophylactic 1-year treatment. Elderly TGF mice featured cerebrovascular dysfunction that was not remedied with NAC. In contrast, pioglitazone prevented or reversed this deficit, and rescued the impaired neurovascular coupling response to whisker stimulation, although it failed to normalize the vascular structure. In aged TGF mice, neuronal and cognitive indices-the stimulus-evoked neurometabolic response, cortical cholinergic innervation, and spatial memory in the Morris water maze-were intact. Our findings show that impaired brain hemodynamics and cerebrovascular function are not accompanied by memory impairment in this model. Conceivably in AD, they constitute aggravating factors against a background of aging and underlying pathology. Our data further highlight the ability of pioglitazone to protect the cerebrovasculature marked by TGF-b1 increase, aging, fibrosis, and antioxidant resistance, thus of high relevance for AD patients.

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“…The images were reconstructed using a maximum intensity algorithm and the population averages generated using the approach described elsewhere. 26 Regions of interest were drawn on the somatosensory cortices and the magnitude of activation expressed as the ratio of […”

Section: F]fluoro-2-deoxy-d-glucose-petmentioning

confidence: 99%

Transgenic Mice Overexpressing APP and Transforming Growth Factor-β1 Feature Cognitive and Vascular Hallmarks of Alzheimer's Disease

Ongali

Nicolakakis

Lecrux

et al. 2010

The American Journal of Pathology

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High brain levels of amyloid-␤ (A␤) and transforming growth factor-␤1 (TGF-␤1) have been implicated in the cognitive and cerebrovascular alterations of Alzheimer's disease (AD). We sought to investigate the impact of combined increases in A␤ and TGF-␤1 on cerebrovascular, neuronal, and mnemonic function using transgenic mice overproducing these peptides (A/T mice). In particular, we measured cerebrovascular reactivity, evoked cerebral blood flow and glucose uptake during brain activation, cholinergic status, and spatial memory, along with cerebrovascular fibrosis, amyloidosis, and astrogliosis, and their evolution with age. An assessment of perfusion and metabolic responses was considered timely, given ongoing efforts for their validation as AD biomarkers. Relative to wild-type littermates, A/T mice displayed an early progressive decline in cerebrovascular dilatory ability, preserved contractility, and reduction in constitutive nitric oxide synthesis that establishes resting vessel tone. Altered levels of vasodilator-synthesizing enzymes and fibrotic proteins, resistance to antioxidant treatment, and unchanged levels of the antioxidant enzyme, superoxide dismutase-2, accompanied these impairments. A/T mice featured deficient neurovascular and neurometabolic coupling to whisker stimulation, cholinergic denervation, cerebral and cerebrovascular A␤ deposition, astrocyte activation , and impaired Morris water maze performance , which gained severity with age. The combined A␤-and TGF-␤1-driven pathology recapitulates salient cerebrovascular, neuronal, and cognitive AD landmarks and yields a versatile model toward highly anticipated diagnostic and therapeutic tools for patients featuring A␤ and TGF-␤1 increments.

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Longitudinal neuroanatomical changes determined by deformation-based morphometry in a mouse model of Alzheimer's disease

Cited by 136 publications

References 51 publications

Behavioral and Neuroanatomical Phenotypes in Mouse Models of Autism

Behavioral and Neuroanatomical Phenotypes in Mouse Models of Autism

Intact Memory in TGF-β1 Transgenic Mice Featuring Chronic Cerebrovascular Deficit: Recovery with Pioglitazone

Transgenic Mice Overexpressing APP and Transforming Growth Factor-β1 Feature Cognitive and Vascular Hallmarks of Alzheimer's Disease

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