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1. PLoS One. 2010 Jan 19;5(1):e8762.

Progression of Parkinson's disease pathology is reproduced by intragastric
administration of rotenone in mice.

Pan-Montojo F, Anichtchik O, Dening Y, Knels L, Pursche S, Jung R, Jackson S,
Gille G, Spillantini MG, Reichmann H, Funk RH.

Institute of Anatomy, Medical Faculty Carl Gustav Carus, Dresden University of
Technology, Dresden, Germany. pan-montojo@mpi-cbg.de

In patients with Parkinson's disease (PD), the associated pathology follows a
characteristic pattern involving inter alia the enteric nervous system (ENS), the
dorsal motor nucleus of the vagus (DMV), the intermediolateral nucleus of the
spinal cord and the substantia nigra, providing the basis for the
neuropathological staging of the disease. Here we report that intragastrically
administered rotenone, a commonly used pesticide that inhibits Complex I of the
mitochondrial respiratory chain, is able to reproduce PD pathological staging as
found in patients. Our results show that low doses of chronically and
intragastrically administered rotenone induce alpha-synuclein accumulation in all
the above-mentioned nervous system structures of wild-type mice. Moreover, we
also observed inflammation and alpha-synuclein phosphorylation in the ENS and
DMV. HPLC analysis showed no rotenone levels in the systemic blood or the central
nervous system (detection limit [rotenone]<20 nM) and mitochondrial Complex I
measurements showed no systemic Complex I inhibition after 1.5 months of
treatment. These alterations are sequential, appearing only in synaptically
connected nervous structures, treatment time-dependent and accompanied by
inflammatory signs and motor dysfunctions. These results strongly suggest that
the local effect of pesticides on the ENS might be sufficient to induce PD-like
progression and to reproduce the neuroanatomical and neurochemical features of PD
staging. It provides new insight into how environmental factors could trigger PD
and suggests a transsynaptic mechanism by which PD might spread throughout the
central nervous system.

PMCID: PMC2808242
PMID: 20098733 [PubMed - indexed for MEDLINE]