Work

Intraneuronal Aggregate Formation and Cell Death after Viral Expression of Expanded Polyglutamine Tracts in the Adult Rat Brain

Year: 2000

Type: article

Abstract: Expanded polyglutamine (polyQ) tracts have been linked to a new class of human disease characterized by psychiatric/motor syndromes associated with specific patterns of neurodegeneration. We have used a direct viral approach to locally express expanded polyglutamine tracts fused to the green fluorescent protein (97Q-GFP) in the adult rat brain. We show that intrastriatal expression of 97Q-GFP causes the rapid formation of fibrillar, cytoplasmic, and ubiquitinated nuclear aggregates in neurons. 97Q-GFP expression also results in a specific temporal pattern of cell death in the striatum. Co-infection studies suggest that high level 97Q-GFP-expressing cells die during the first month, whereas low level 97Q-GFP-expressing neurons persist for up to 6 months after infection. These data indicate that cumulative expression of polyQ repeats throughout the life of the animal is not required to induce neuronal death, but rather acute overexpression of polyQ is toxic to adult neurons in vivo.

Source: Journal of Neuroscience

DOI: 10.1523/jneurosci.20-01-00219.2000

Authors: Marie-Claude Senut, Steven T. Suhr, Brian Kaspar, Fred H. Gage

Institution: Salk Institute for Biological Studies

Language: English

Topic: Genetic Neurodegenerative Diseases

Subfield: Cellular and Molecular Neuroscience

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Funders: Hereditary Disease Foundation, National Institute on Aging