The fruit fly (Drosophila melanogaster) is a very interesting model system for studying cellular pathways that are important in PD. Here you can find an interesting review on this topic: http://www.hindawi.com/journals/pd/2011/520640/

In Drosophila rotenone has mainly been used to model PD.

Best regards, Christian

Dear Christian,

Thank you so much for your response to my question. I intend using mice. Which of the models do you recommend

Hi,

rotenone has been used in several models, indeed including the fly, also it's an actual environmental hazard (could contribute to increased incidence of PD among farmers).

Hello Abdulbasit,

I am sorry but I have not worked on PD in mice. Therefore I have no recommendation which mouse model is best for studying PD...

Maybe some other researchers can give you some insights?

Good luck!

Hi Abdulbasit

I second your choice of using an MPTP mouse model. One of our colleagues at my previous institution has used this mouse model successfully for inducing PD.

Please see this link for more information. http://www.ncbi.nlm.nih.gov/pubmed/?term=20405343

Best,

Chandana

 If you want to do also an in vitro study I can suggest LUHMES cell line -  a modern and robust model cells easily and equally differentiating into dopaminergic neurons. If you consider only mice than a proper decision of a model toxin is important.

 MPTP is lipofilic and will cross the blood brain barrier. Rotenone is a direct inhibitor of complex I. Six hydroxydopamine is a potent oxidative stress inducer but must be administred intrastratial because it will not cross the blood brain barrier. Toxin alone will not lead to an apearence of Lewy bodies....

There are plenty of good reviews on animal toxin model of PD. One of them which may be useful for you:

Toxin models of mitochondrial dysfunction in Parkinson's disease.

Martinez TN, Greenamyre JT.

Antioxid Redox Signal. 2012 May 1;16(9):920-34. doi: 10.1089/ars.2011.4033. Epub 2011 Jul 12. Review.

 I work on some aspects of PD in an in vitro model and so I am not experienced with animal models but to my knowladge MPTP model is most commonly used in rodents. Good Luck!

6-OHDA is the classic and oft utilized toxin-based animal model of PD. A lot of information on the behavioral, biochemical, and physiological effects of dopamine in the CNS has been derived from this model.

6-OHDA does not cross blood brain barrier, so we have to inject in medial forebrain.

 by a combined effect of ROS and quinones, 6-OHDA destroys catecholaminergic neurons  and thus induces inflammation in the brain. The most common use of 6-OHDA is via unilateral injection into the rat medial forebrain bundle. Injection of 6-OHDA into the SNpc kills approximately 60% of the tyrosine hydroxylase- (TH-) containing neurons in this area of the rodent brain with subsequent loss of TH-positive terminals in the striatum. it is widely use in rodent (Rat) to induce PD.

Where as MPTP is highly lipophilic and after systemic administration rapidly crosses the blood-brain barrier. Once in the brain, MPTP enters astrocytes and is metabolized into MPP+, its active metabolite, by monoamine oxidase-B (MAO-B).

MPTP is used mainly in nonhuman primates and mice but has also been used in many other species such as dogs and cats,

so you can go for both MPTP and 6-OHDA induced PD

• It all depends on what you are trying to study and/or accomplish.  There is no one best model of Parkinson's disease. Different models are good at reproducing various features of the disease.  If you want to test dopamine-replacement therapy then MPTP works well as it greatly reduces striatal dopamine, but if you are looking at disease progression is may not be very helpful.  The alpha synuclein models do a nice job of evaluating the impact of synculein, but most don't cause a robust loss of dopamine (some do though).  There are interesting models with altered mitochondrial function (genetic or rotenone), and reduced dopamine storage. 6-OHDA is similar to MPTP in that it wipes out the dopamine neurons, good for studying effects of depleted dopamine. They key is not to over interpret your results. You are studying what you model models, nothing more.

Dear Gary,

Thank you for your contribution. I am interested in oxidative stress and inflammation. So which do you think serves best

There is unfortunately no model that recapitulate PD. If your ultimate aim is to develop therapeutics you require a model with quantifiable features. Toxic models is better, especially MPTP. They are quick to develop and Dopamine and TH+ cells are good markers. Different dosing paradigm of MPTP also allows calibration of beneficial effects against drug candidates and gives different effects with respect to mode of cell death. However you require special training and hazard suite to work with MPTP. Genetic models excellent chronic models, especially SNCA, however cell death and DA depletion  are modest. Each genetic model gives ample scope for a study on oxidative stress and inflammation. I would expect the outcome would be binding only to that specific model rather than PD in general.  I would recommend a chronic MPTP pump model and SNCA mouse model and compare. You will get a better answers from this article (Beal MF. Parkinson's disease: a model dilemma. Nature. 2010 Aug 26;466(7310):S8-10. doi: 10.1038/466S8a. PubMed PMID: 20739935).