title: Intraneuronal aggregate formation and cell death after viral expression of expanded polyglutamine tracts in the adult rat brain.
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.
authors.affiliation: Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
authors.forename: M C
authors.initials: MC
authors.lastname: Senut
authors.forename: S T
authors.initials: ST
authors.lastname: Suhr
authors.forename: B
authors.initials: B
authors.lastname: Kaspar
authors.forename: F H
authors.initials: FH
authors.lastname: Gage
mesh_terms: D000256:Adenoviridae; D000257:Adenoviridae Infections; D000367:Age Factors; D000818:Animals; D000906:Antibodies; D017209:Apoptosis / Q000235:genetics; D001921:Brain / Q000166:cytology; D002449:Cell Aggregation / Q000502:physiology; D002467:Cell Nucleus / Q000473:pathology; D003342:Corpus Striatum / Q000473:pathology / Q000503:physiopathology; D003593:Cytoplasm / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D015967:Gene Expression Regulation, Viral; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D006816:Huntington Disease / Q000473:pathology / Q000503:physiopathology; D020287:In Situ Nick-End Labeling; D002479:Inclusion Bodies / Q000378:metabolism / Q000473:pathology; D007202:Indicators and Reagents / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics / Q000276:immunology; D008845:Microinjections; D009410:Nerve Degeneration / Q000473:pathology* / Q000503:physiopathology; D009474:Neurons / Q000166:cytology* / Q000821:virology; D010455:Peptides / Q000235:genetics*; D051381:Rats; D011916:Rats, Inbred F344; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D013378:Substantia Nigra / Q000473:pathology / Q000503:physiopathology; D019076:Transgenes / Q000235:genetics / Q000276:immunology; D014452:Ubiquitins / Q000378:metabolism
chemical_list: D000906:Antibodies; D007202:Indicators and Reagents; D008164:Luminescent Proteins; D010455:Peptides; D011993:Recombinant Fusion Proteins; D014452:Ubiquitins; D049452:Green Fluorescent Proteins; C097188:polyglutamine