Tauopathy in Drosophila : Neurodegeneration Without Neurofibrillary Tangles-Reference-Cited by-同舟云学术

Tauopathy in Drosophila : Neurodegeneration Without Neurofibrillary Tangles

Published:2001-07-27 Issue:5530 Volume:293 Page:711-714
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Wittmann Curtis W.¹,Wszolek Matthew F.¹,Shulman Joshua M.¹,Salvaterra Paul M.²,Lewis Jada³,Hutton Mike³,Feany Mel B.¹

Affiliation:

1. Department of Pathology, Division of Neuropathology, Brigham and Women's Hospital and Harvard Medical School, 221 Longwood Avenue, Room 514, Boston, MA 02115, USA.

2. Division of Neurosciences, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA.

3. Mayo Clinic Jacksonville, Jacksonville, FL 32224, USA.

Abstract

The microtubule-binding protein tau has been implicated in the pathogenesis of Alzheimer's disease and related disorders. However, the mechanisms underlying tau-mediated neurotoxicity remain unclear. We created a genetic model of tau-related neurodegenerative disease by expressing wild-type and mutant forms of human tau in the fruit fly Drosophila melanogaster . Transgenic flies showed key features of the human disorders: adult onset, progressive neurodegeneration, early death, enhanced toxicity of mutant tau, accumulation of abnormal tau, and relative anatomic selectivity. However, neurodegeneration occurred without the neurofibrillary tangle formation that is seen in human disease and some rodent tauopathy models. This fly model may allow a genetic analysis of the cellular mechanisms underlying tau neurotoxicity.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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5. Heads from adult flies at 1 day after eclosion were fixed in formalin and embedded in paraffin and 4-μm frontal sections were prepared. Serial sections were cut through the entire brain placed on a single glass slide and stained with hematoxylin and eosin (H&E) Bielschowsky (Fig. 2 A and B) or bodian silver stains. H&E sections highlight the normal arrangement of basophilic neuronal and glial cell bodies in the outer cortical layer and the inner eosinophilic neuropil regions. Silver stains label axonal projections and demonstrate anatomic features. The quantitative analysis in Fig. 2E was performed on 4-μm-thick paraffin sections stained with H&E. The number of degenerating neurons and the number of vacuoles measuring greater than 5 μm in diameter were counted in five well-oriented frontal sections between the level of the fan-shaped body and the calyx of the mushroom body. Sections from at least five individual brains were examined per time point for each genotype.

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