Premium
Reproducible nigral cell loss after systemic proteasomal inhibitor administration to rats
Author(s) -
Zeng BaiYun,
Bukhatwa Salma,
Hikima Atsuko,
Rose Sarah,
Jenner Peter
Publication year - 2006
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.20932
Subject(s) - substantia nigra , dorsal motor nucleus , locus ceruleus , dopaminergic , tyrosine hydroxylase , locus coeruleus , medicine , endocrinology , chemistry , dopamine , neuroscience , pharmacology , biology , vagus nerve , central nervous system , stimulation
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 α‐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. Ann Neurol 2006;60:248–252