Non-invasive imaging of neuropathology in a rat model of alpha-synuclein overexpression.
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.
Lauwers
Erwin
E
Laboratory for Neurobiology and Gene Therapy, K.U. Leuven, Leuven, Belgium.
Bequé
Dirk
D
Van Laere
Koen
K
Nuyts
Johan
J
Bormans
Guy
G
Mortelmans
Luc
L
Casteels
Cindy
C
Vercammen
Linda
L
Bockstael
Olivier
O
Nuttin
Bart
B
Debyser
Zeger
Z
Baekelandt
Veerle
V
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*
D050483:Dopamine Plasma Membrane Transport Proteins; D051844:alpha-Synuclein