Abstract
APP23 transgenic mice overexpressing amyloid precursor protein (APP751) reproduce neuropathological changes associated with Alzheimer's disease such as high levels of amyloid plaques, cerebral amyloid angiopathy, and associated vascular pathologies. Functional magnetic resonance imaging (fMRI) was applied to characterize brain functionality in these mice through global pharmacological stimulation. The cerebral hemodynamic response to infusion of the GABA(A) antagonist bicuculline was significantly reduced in aged APP23 mice compared with age-matched wild-type littermates. This is in part attributable to a compromised cerebrovascular reactivity, as revealed by the reduced responsiveness to vasodilatory stimulation by acetazolamide. The study shows that fMRI is a sensitive tool to phenotype genetically engineered animals modeling neuropathologies.
MeSH terms
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Acetazolamide / pharmacology
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Age Factors
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Alzheimer Disease / genetics
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Alzheimer Disease / physiopathology*
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Amyloid beta-Protein Precursor / biosynthesis*
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Amyloid beta-Protein Precursor / genetics
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Animals
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Bicuculline / pharmacology
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Body Weight
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Brain / blood supply*
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Brain / drug effects
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Brain / physiopathology*
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Carbonic Anhydrase Inhibitors / pharmacology
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Cerebrovascular Circulation / drug effects
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Cerebrovascular Circulation / genetics
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Disease Models, Animal
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Dose-Response Relationship, Drug
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Drug Resistance / genetics
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GABA Antagonists / pharmacology
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GABA-A Receptor Antagonists
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Hemodynamics* / drug effects
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Hemodynamics* / genetics
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Humans
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Magnetic Resonance Imaging
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Mice
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Mice, Transgenic
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Phenotype
Substances
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Amyloid beta-Protein Precursor
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Carbonic Anhydrase Inhibitors
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GABA Antagonists
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GABA-A Receptor Antagonists
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Acetazolamide
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Bicuculline