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

• Published in: The Journal of neuroscience 2000-01, Vol.20 (1), p.219-229
• Main Authors: Senut, Marie-Claude, Suhr, Steven T, Kaspar, Brian, Gage, Fred H
• Format: Article
• Language: English
• Subjects: Adenoviridae; Adenoviridae Infections; Age Factors; Animals; Antibodies; Apoptosis - genetics; Brain - cytology; Cell Aggregation - physiology; Cell Nucleus - pathology; Corpus Striatum - pathology; Corpus Striatum - physiopathology; Cytoplasm - pathology; Disease Models, Animal; Female; Gene Expression Regulation, Viral; Gene Transfer Techniques; Genes, Reporter; Green Fluorescent Proteins; Huntington Disease - pathology; Huntington Disease - physiopathology; In Situ Nick-End Labeling; Inclusion Bodies - metabolism; Inclusion Bodies - pathology; Indicators and Reagents - metabolism; Luminescent Proteins - genetics; Luminescent Proteins - immunology; Microinjections; Nerve Degeneration - pathology; Nerve Degeneration - physiopathology; Neurons - cytology; Neurons - virology; Peptides - genetics; polyglutamine; Rats; Rats, Inbred F344; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - immunology; Substantia Nigra - pathology; Substantia Nigra - physiopathology; Transgenes - genetics; Transgenes - immunology; Ubiquitins - metabolism
• ISSN: 0270-6474; 1529-2401; 1529-2401
• DOI: 10.1523/jneurosci.20-01-00219.2000

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.