Reproducible nigral cell loss after systemic proteasomal inhibitor administration to rats.
Systemic administration of proteasomal inhibitors to rats has been proposed as producing progressive nigral dopaminergic cell loss and impairment of motor function, although this has proved difficult to reproduce. We report reproducible loss of tyrosine hydroxylase-positive cells in substantia nigra and decrease in locomotor activity by proteasomal inhibitor injection in rats up to 10 months after treatment. Dopaminergic cell death was accompanied by the appearance of ubiquitin and alpha-synuclein-positive inclusions in the substantia nigra in these rats. Neuronal loss was also observed in the locus ceruleus, raphe nuclei, and dorsal motor nucleus of the vagus, verifying that proteasomal inhibition produces a relevant model of Parkinson's disease.
Zeng
Bai-Yun
BY
Neurodegenerative Diseases Research Centre, School of Health and Biomedical Sciences, King's College, London, United Kingdom.
Bukhatwa
Salma
S
Hikima
Atsuko
A
Rose
Sarah
S
Jenner
Peter
P
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002452:Cell Count; D016923:Cell Death / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D015853:Cysteine Proteinase Inhibitors / Q000633:toxicity*; D004298:Dopamine / Q000502:physiology; D005260:Female; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D002479:Inclusion Bodies / Q000473:pathology; D007279:Injections, Subcutaneous; D008297:Male; D009043:Motor Activity; D009457:Neuroglia / Q000187:drug effects; D009842:Oligopeptides / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D013378:Substantia Nigra / Q000201:enzymology / Q000473:pathology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism; D051844:alpha-Synuclein / Q000378:metabolism
D015853:Cysteine Proteinase Inhibitors; D009842:Oligopeptides; D025801:Ubiquitin; D051844:alpha-Synuclein; C090535:benzyloxycarbonyl-isoleucyl-glutamyl(O-tert-butyl)-alanyl-leucinal; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine