Intraneuronal aggregate formation and cell death after viral expression ofexpanded polyglutamine tracts in the adult rat brain

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