Aβ1–40-related reduction in functional hyperemia in mouse neocortex during somatosensory activation
| Autor: | Karen H. Ashe, Kiyoshi Niwa, Linda H. Younkin, David Westaway, Costantino Iadecola, Steven G. Younkin, Christine Ebeling, George A. Carlson, Sherry Turner |
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| Rok vydání: | 2000 |
| Předmět: |
Male
Genetically modified mouse medicine.medical_specialty Transgene Hyperemia Mice Transgenic Biology Somatosensory system medicine.disease_cause Presenilin Hypercapnia Pathogenesis Amyloid beta-Protein Precursor Mice Physical Stimulation Internal medicine mental disorders Laser-Doppler Flowmetry Presenilin-1 medicine Animals Humans Mutation Amyloid beta-Peptides Multidisciplinary Neocortex Membrane Proteins Somatosensory Cortex Biological Sciences Peptide Fragments Cell biology Mice Inbred C57BL Glucose Endocrinology medicine.anatomical_structure Cerebral blood flow Touch Cerebrovascular Circulation Vibrissae Female |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.97.17.9735 |
| Popis: | Peptides derived from proteolytic processing of the beta-amyloid precursor protein (APP), including the amyloid-beta peptide (Abeta), play a critical role in the pathogenesis of Alzheimer's dementia. We report that transgenic mice overexpressing APP and Abeta have a profound attenuation in the increase in neocortical blood flow elicited by somatosensory activation. The impairment is highly correlated with brain Abeta concentration and is reproduced in normal mice by topical neocortical application of exogenous Abeta1-40 but not Abeta1-42. Overexpression of M146L mutant presenilin-1 in APP mice enhances the production of Abeta1-42 severalfold, but it does not produce a commensurate attenuation of the hyperemic response. APP and Abeta overexpression do not diminish the intensity of neural activation, as reflected by the increase in somatosensory cortex glucose usage. Thus, Abeta-induced alterations in functional hyperemia produce a potentially deleterious mismatch between substrate delivery and energy demands imposed by neural activity. |
| Databáze: | OpenAIRE |
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