Dear community,
For my master's project, I want to design an experiment that will asses the efficiency of an antioxidant to stop/restore mitochondrial oxidative stress/redox balance in a PD mouse model, in both early and later stages of the disease. Redox balance will be assessed by using a roGFP lifetime measurements in vivo.
I was thinking to use MPTP model, due to it's effect on the mitochondria, simplicity and practicality. However I heard that this model can be difficult and dangerous to work with and might kill the mice faster than the experiment will end.
There is 6-ohda model, but I was reticent to use it because it has to be injected into the brain directly (which I believe might interfere with my fluorescence measurements) and the mechanisms behind it are not fully understood.
I would highly appreciate if anyone could share their experiences about working with these(or maybe other) models and give me an appreciation of their suitability in regard to my research question.
Thank you!
Hi,
I have used MPTP to model PD in an acute set up. The dosage i used is 30 mg/kg two i.p. injections 16 hrs apart, then behavioral assay on 6th day and on 7th day sacrifice and tissue collection for downstream analysis. I never faced mice death as such. For chronic models, please refer to published articles.
Hope this would help.
Best,
Alpana
Hi Ecaterina Savenco
* 6-OHDA and MPTP model are the most widely used animal models for screening of drugs against Parkinson's disease.
* 6-OHDA model requires stereotaxic surgery expertise, much more complex and mortality is high. Produces free radicals that acts as potent inhibitor of the mitochondrial respiratory chain complexes I and IV. Neuroinflammation and neuronal death may progress to other regions of the brain if surgery is not perfectly.
* Whereas MPTP model is simple, 25mg/kg in C57BL/6 mice for 5 days intraperitoneal. MPTP is metabolized into the toxic cation 1-methyl-4-phenylpyridinium (MPP+) by the enzyme monoamine oxidase B (MAO-B) of glial cells, specifically astrocytes and accumulates within SNpc DA neurons, where it inhibits ATP production and stimulates superoxide radical formation.
So, you can study mitochondrial dynamics, dysfunction and redox changes according to your study design.
Animal mortality would be around 10-15%. Yes MPTP is quite dangerous to work with, however I have been using the same from the past 6 years, I have attached the paper that discusses in detail, precautions needed to work with MPTP. If you can these necessary precautions, there is nothing to worry about more then.
* I would recommend you the MPTP induced PD model for your work.
Hope it works.
Thanks
Samir Ranjan
Ref:
1. https://www.nature.com/articles/nprot.2006.342
2. https://www.nature.com/articles/s41418-018-0124-5
In addition to the already proposed models, we used the injection of rotenone subcutaneously at a dose of 1.75 mg/kg into rats. Rotenone was dissolved in DMSO and a special interlipid.
Alpana Singh , Samir Ranjan Panda Natalya Venediktova Thank you all very much for your valuable input! I appreciate it a lot.
The best Parkinson's mouse model for your research depends on the specific aims of your study. Commonly used models include the MPTP-lesioned mouse, the Rotarod mouse, the SNCA transgenic mouse, and the α-synuclein overexpressing mouse. You should consult with a pre-clinical specialist or a research lab that specializes in Parkinson's research to determine which model is most appropriate for your study.