title: Non-invasive imaging of neuropathology in a rat model of alpha-synuclein overexpression.
abstract: Parkinson's disease is a neurodegenerative disorder affecting the dopaminergic neurons in the substantia nigra. Aggregation of alpha-synuclein appears to play a central role in the pathogenesis. Novel animal models for neurodegeneration have been generated by lentiviral vector-mediated locoregional overexpression of disease-associated genes in the adult brain. We have used lentiviral vectors to overexpress a clinical mutant of alpha-synuclein, A30P, in the rat substantia nigra. This overexpression induced time-dependent cytoplasmic and neuritic accumulation of alpha-synuclein and neurodegeneration. A subgroup of the rats developed asymmetric rotational behavior after administration of amphetamine. In addition, these animals displayed reduced dopamine transporter binding visualized by 123I-FP-CIT microSPECT imaging. The behavioral and microSPECT data were validated by histological analysis. There was a strong correlation between the reduction of dopaminergic neurons in the substantia nigra and the reduction of dopamine transporter binding in the striatum. MicroSPECT imaging enables non-invasive imaging of the neurodegeneration allowing longitudinal follow-up in this new animal model for Parkinson's disease and the evaluation of neuroprotective drugs.
authors.affiliation: Laboratory for Neurobiology and Gene Therapy, K.U. Leuven, Leuven, Belgium.
authors.forename: Erwin
authors.initials: E
authors.lastname: Lauwers
authors.forename: Dirk
authors.initials: D
authors.lastname: Bequé
authors.forename: Koen
authors.initials: K
authors.lastname: Van Laere
authors.forename: Johan
authors.initials: J
authors.lastname: Nuyts
authors.forename: Guy
authors.initials: G
authors.lastname: Bormans
authors.forename: Luc
authors.initials: L
authors.lastname: Mortelmans
authors.forename: Cindy
authors.initials: C
authors.lastname: Casteels
authors.forename: Linda
authors.initials: L
authors.lastname: Vercammen
authors.forename: Olivier
authors.initials: O
authors.lastname: Bockstael
authors.forename: Bart
authors.initials: B
authors.lastname: Nuttin
authors.forename: Zeger
authors.initials: Z
authors.lastname: Debyser
authors.forename: Veerle
authors.initials: V
authors.lastname: Baekelandt
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D003342:Corpus Striatum / Q000000981:diagnostic imaging* / Q000378:metabolism*; D004195:Disease Models, Animal; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D005500:Follow-Up Studies; D010300:Parkinson Disease / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D011877:Radionuclide Imaging; D051381:Rats; D017208:Rats, Wistar; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism*
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D051844:alpha-Synuclein