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Reproducible nigral cell loss after systemic proteasomal inhibitor administration to rats

Research output: Contribution to journalArticle

B Y Zeng, S Bukhatwa, A Hikima, S Rose, P Jenner

Original languageEnglish
Pages (from-to)248 - 252
Number of pages5
JournalAnnals of Neurology
Volume60
Issue number2
DOIs
Publication statusPublished - Aug 2006

King's Authors

Abstract

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 (x-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

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