RT info:eu-repo/semantics/article
T1 A highly reproducible rotenone model of Parkinson's disease
A1 Cannon, Jason R.
A1 Tapias, Victor
A1 Na, Hye Mee
A1 Honick, Anthony S.
A1 Drolet, Robert E.
A1 Greenamyre, J. Timothy
AB The systemic rotenone model of Parkinson's disease (PD) accurately replicates many aspects of the pathology of human PD and has provided insights into the pathogenesis of PD. The major limitation of the rotenone model has been its variability, both in terms of the percentage of animals that develop a clear-cut nigrostriatal lesion and the extent of that lesion. The goal here was to develop an improved and highly reproducible rotenone model of PD. In these studies, male Lewis rats in three age groups (3, 7 or 12-14 months) were administered rotenone (2.75 or 3.0 mg/kg/day) in a specialized vehicle by daily intraperitoneal injection. All rotenone-treated animals developed bradykinesia, postural instability, and/or rigidity, which were reversed by apomorphine, consistent with a lesion of the nigrostriatal dopamine system. Animals were sacrificed when the PD phenotype became debilitating. Rotenone treatment caused a 45% loss of tyrosine hydroxylase-positive substantia nigra neurons and a commensurate loss of striatal dopamine. Additionally, in rotenone-treated animals, alpha-synuclein and poly-ubiquitin positive aggregates were observed in dopamine neurons of the substantia nigra. In summary, this version of the rotenone model is highly reproducible and may provide an excellent tool to test new neuroprotective strategies.
SN 0969-9961
YR 2009
FD 2009
LK https://uvadoc.uva.es/handle/10324/63873
UL https://uvadoc.uva.es/handle/10324/63873
LA eng
NO Neurobiology of Disease, Mayo 2009, vol. 34, n. 2, p. 279-290
NO Producción Científica
DS UVaDOC
RD 07-ago-2024