0 votes

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

Francisco J. Pan-Montojo¹, Oleg Anichtchik², Yanina Dening³, Lilla Knells³, Stefan Pursche³, Roland Jung³, Gabriele Gille³, Maria Grazia Spillantini², Heinz Reichmann³ & Richard H. W. Funk³

Correspondence: (Login to view email address)

1. TU Dresden/ International Max-Planck Research School
2. University of Cambridge
3. TU Dresden

DOC (17.5 MB) PDF (11.2 MB)

Document Type:

Manuscript

Date:

Received 19 June 2009 22:43 UTC; Posted 22 June 2009

Subjects:

Neuroscience

Tags:

• Parkinson's Disease
• Enteric Nervous System
• Lewy Bodies
• alpha-synuclein

Abstract:

In Parkinson’s disease patients pathology follows a characteristic pattern involving inter alia the enteric nervous system, the dorsal motor nucleus of the vagus, 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 mitochondrial Complex I, is able to reproduce PD pathological staging as found in patients. Our results show that low doses of chronically and intragastrically administered rotenone induce PD pathology in all the above-mentioned nervous system structures in wild-type mice. Interestingly, HPLC analysis showed no rotenone levels in the systemic blood or the central nervous system (CNS) (detection limit [rotenone]<20nM), suggesting that rotenone is detoxified by the liver. 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 progression and to reproduce the neuroanatomical and neurochemical features of PD staging. Thus, providing new insight into how environmental factors could trigger PD and suggesting a transsynaptic mechanism by which PD might propagate to and through the CNS.

Discussion

Votes:

0 votes

(Login to vote)

Comments:

0 comments

(Login to post a comment)

Share:

(Login to share with a colleague)

Additional information

License:

This document is licensed to the public under the Creative Commons Attribution 3.0 License

How to cite this document:

Pan-Montojo, Francisco, Anichtchik, Oleg, Dening, Yanina, Knells, Lilla , Pursche, Stefan, Jung, Roland , Gille, Gabriele, Spillantini, Maria Grazia, Reichmann, Heinz, and Funk, Richard. Progression of Parkinson’s disease pathology is reproduced by intragastric administration of rotenone in mice . Available from Nature Precedings <http://hdl.handle.net/10101/npre.2009.3352.1> (2009)

Version info:

Other versions of this document in Nature Precedings

Version number	Document title	Date
v2	Posted 22 June 2009

Other versions of this document elsewhere on the web

None known.

Submit a new version link