coffee's caffeine effects on parkinson's disease

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sciencerocks18
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coffee's caffeine effects on parkinson's disease

Post by sciencerocks18 »

Hello science experts,

My name is Hareshan Suntharalingam, and I want to do a science fair project on how the adenosine A2A receptors antagonists found in the caffeine from coffee can help treat parkinson's disease. I have already completed a lot of my
preliminary research. I am looking for ways to prove my theory without conducting any tests on humans.
I am currently in grade 9 so I want to come up with an experimental procedure quite simple. Can you suggest
a few ideas to prove this theory. I am looking forward to your response.
I would like to thank you for all your time and support!
I will be very greatly appreciate any source of information that would contribute to my science project.

Thanks
Hareshan
PharmaMan
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Re: coffee's caffeine effects on parkinson's disease

Post by PharmaMan »

Hi Hareshan,

This is a very interesting project indeed. If you don't mind me asking, but what kinds of data have you generated already for your hypothesis? This will give us an idea as to what some next steps might be for your project. Some of the last major experiments for many different projects within pharmacology will typically be in vivo studies with rats, mice, etc. If you are able to demonstrate your mechanism partially in vivo, it will provide a lot of credibility to your studies. Do you happen to have any connections where you may be able to do such studies? Note that this will have to be done at a university-level laboratory with specialized animal facilities.

If not, perhaps there are other in vitro experiments that we can help you to design. Let us know more about your project and we'll be happy to help. This definitely sounds like a cool project.

Best,
Pharma
sciencerocks18
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Re: coffee's caffeine effects on parkinson's disease

Post by sciencerocks18 »

Hello,

Thanks a lot for your suggestions. I found out that parkinson's disease is caused by the degeneration of a part
of the brain known as the Basal Ganglia and also because of the loss of the production of the neurotransmitter
dopamine.
From researching I also realized that studies in animal models of Parkinson’s disease suggest that caffeine may protect dopaminergic neurons (neurons that produce the neurotransmitter dopamine) by acting as an adenosine A2A-receptor antagonist in the brain.
I had read through a lot of studies that have been conducted on humans. The studies suggest that caffeine is more effective in men and it prevents them from developing parkinson's disease more in comparison to women.
I am currently in grade 9 and my science fair is in the middle of April so I don't think that I will get access to a university laboratory to conduct the experiment and I don't think that I will have mice/rats in my school or get the permission in time to do so either.
Is it possible that you can suggest potential vitro experimental procedures to prove my theory. Can you also add some reliable online sources which have examples of vitro/vivo experiments similar to my study?
I need all the help that I can get as soon as possible!
However, I will still try to get hold of some university level laboratories and I will try talking to them about my project too.
I will greatly appreciate any source of assistance and support that you can offer!!!

From
Hareshan
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Re: coffee's caffeine effects on parkinson's disease

Post by PharmaMan »

Hi Hareshan,

Thanks for getting back with the information. A good experiment to show this effect would actually be an in vivo study using models of Parkinson's disease. In such an experiment, a mouse (or other model organism) that has an inducible mutation in the A2A receptor could be used to show a delay in the onset of Parkinson's. I understand the dilemma that there isn't much time, and these are definitely complex experiments that can require many months to complete.

In vitro, you could show that caffeine acts as a receptor antagonist by analyzing the effects on the downstream signaling pathway in cultured neurons. Typically when we analyze different agents in the lab and their effects on certain signaling pathways, we will look at how the activation of downstream targets (such as kinases, etc.) are affected. You could perform a similar experiment; however, I feel that this would also best be done in a university-level laboratory that routinely works with these types of systems.

I did find a review article on PubMed:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4115368/

There are many links within here to different studies (scroll to the section specifically about Parkinson's; one of the free research articles linked is the Sonsalla et al paper). I would recommend either PubMed or Google Scholar to search for any studies that might interest you for this project.

It seems that you have done a good amount of research already for this project; however, I think that the experiments that need to be done will have to be using these cell systems (cultured neurons) or even animal models. Let us know what you think. If there is a way that you may be able to get access to facilities that could help you to do these experiments, then that would likely be the best way.

Hope this helped,
Pharma
sciencerocks18
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Re: coffee's caffeine effects on parkinson's disease

Post by sciencerocks18 »

Hello,

First of all, I would like to thank you for suggesting potential ways to prove how caffeine found in coffee can be used to treat Parkinson's disease. This certainly sounds like an interesting yet simpler way to prove the positive effects of adenosine A2A receptors.

I had read the Pub Med article and it had talked about the DARPP-32 and ERK1/2 signaling pathway. I had difficulty
comprehending what it is and its actual use. Can you please help me understand what they are and how this forms an effective signalling pathway.

How do these signalling pathways exhibit the function of adenosine A2A receptors and represent the levodopa-induced motor fluctuations in the brain?

I am trying to get hold of a University of Toronto professor who specializes in neuroscience and neurodegenerative diseases so that hopefully I can conduct this experiment. Does this experiment require a lot of time and patience to observe how time can impact the results like in a vivo study or can it be completed in a short period of time?

Many more thanks again for being my mentor and assisting me throughout this project.

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Hareshan
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Re: coffee's caffeine effects on parkinson's disease

Post by PharmaMan »

Hi Hareshan,

You're very welcome, we are here to help with any questions you may have. In regards to the PubMed article, I took a look at the linked article that was discussing the DARPP-32 and ERK1/2 signaling pathways. It seems to me that the authors were trying to improve symptoms that occur from use of levodopa (L-DOPA) treatment. Their results seem to suggest that caffeine treatment increases the phosphorylation of DARPP-32, but it decreases the phosphorylation of ERK1/2 (when comparing L-DOPA+caffeine treated rats with L-DOPA-treated rats-both sets of rats being models of Parkinson's). The review article suggests that a decrease in ERK1/2 is beneficial in neuronal cells, but I do not know the functional significance of this.

In essence, a basic signaling pathway that we can construct is that the A2A receptor is linked to modulation of these downstream proteins. In other words, A2A receptor inhibition --> increase in DARPP-32 phosphorylation and a decrease in ERK1/2 phosphorylation (again, when comparing L-DOPA+caffeine to L-DOPA alone). While DARPP-32 seems to be a protein involved in regulating neurotransmitter levels, ERK1/2 is a potent cell-growth stimulating pathway. Linked below are the Wikipedia articles for each if you need more information:

https://en.wikipedia.org/wiki/PPP1R1B

https://en.wikipedia.org/wiki/Extracell ... ed_kinases

These signaling pathways are essentially modulating the adverse effects of L-DOPA treatment. By administering caffeine treatment, the authors are able to downregulate A2A receptor expression, resulting in the changes mentioned above in the signaling pathways. However, this is just one mechanistic study, and there are likely several other pathways that could be involved.

Yes, to complete in vivo experiments can take quite some time. I don't know for a fact since I do not work in neuroscience, but I know that some animal experiments in this field can be quite lengthy (several months to years). The best experiments to do would be to propose a mechanism for how you think A2A receptor inhibition can be beneficial in the treatment of Parkinson's disease, and then carry that out in an in vivo study. However, if this is not possible, cell culture experiments testing your proposed mechanism might be the best that you could do with the time constraints.

Please let us know if you have further questions and what we can do to help.

Best,
Pharma
sciencerocks18
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Re: coffee's caffeine effects on parkinson's disease

Post by sciencerocks18 »

Hello Dr. Pharma,

Thank you very much for elaborating on the vitro experimental procedures and how it can be practically demonstrated.
I have a better understanding of it now. However, I don't think that I can get hold of a university level laboratory in order to conduct this experiment because I have exactly 2 months for the competition. I had e-mailed the professors from the University of Toronto and Queens University that specialize in neurodegenerative diseases but they didn't reply.
Due to the time constrains, I am planning on converting my study into a research project. In order to support my theory, I need a sufficient amount of pictures, diagrams, graphics or animations to explain this experimental procedure in more simple scientific terms. It can be even a flow chart. Can you please suggest some ideas or even send potential graphic images that I can use to support my theory and experimental procedure? I can probably get a picture of the brain and talk about the deficiency of the neurotransmitter dopamine and label the neurodegeneration of the substantia nigra too. Any help that you can offer will be greatly appreciated. I would like to thank you once more for taking your time off your busy schedule to help me out with this science fair project

From
Hareshan
sciencerocks18
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Re: coffee's caffeine effects on parkinson's disease

Post by sciencerocks18 »

Hello,

Do you know anyone that will probably allow me to use a laboratory by any chance for this project or do you have access to any of this specialized equipment in a specialized university laboratory?
I greatly appreciate you for your time and support.

Thanks
Hareshan
sciencerocks18
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Re: coffee's caffeine effects on parkinson's disease

Post by sciencerocks18 »

If you are unable to get hold of a university laboratory, it is alright. I understand how difficult it is to try to do advanced level experiments like this in a short amount of time. If not can you please reply as soon as possible as to some of the ways that I can present my project effectively using visual representations too such as pictures, diagrams, or flow charts.

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Re: coffee's caffeine effects on parkinson's disease

Post by PharmaMan »

Hi Hareshan,

You're very welcome; I'm glad to be of assistance to you! I think your plan is a good one moving forward. To plan, order/breed the necessary animal models, carry out the experiment, and analyze the results, it will take a good amount of time (much longer than 2 months). To illustrate your point, gather the relevant literature for your project. This will include all of the research you have done up to this point about the biology of the disease, neurotransmitters involved, etc. You can have a picture of the brain structures with a text box pointing to the area describing the pathology of the disease.

To give a description of the mechanism of action of the receptor inhibition, what we usually do is to have a signaling diagram that depicts proteins/signaling molecules activating or inhibiting other proteins/signaling molecules either upstream or downstream. Here is an example:

https://www.google.com/search?q=signali ... IKz0VwM%3A

The arrows indicate an activation event, whereas the perpendicular lines indicate an inhibition event. You can have a similar diagram for your project. It would be something along these lines:

Caffeine ---I A2A receptor --> ERK1/2

Obviously, your final diagram will have more components, but we can help once you have all the details together from your previous research. Take note: the arrows and perpendicular lines indicate how the upstream protein normally regulates the protein immediately downstream of it. When you add a drug/inhibitor to the system, although the signaling will change, these arrow/line conventions will still be the same. What will change is that you will show that the drug inhibits the upstream receptor and that is all.

I envision that your final product will be an overview of the disease, followed by a proposed mechanism of treatment. Then you can show a signaling diagram showing how this treatment option works at the molecular level. You can even propose experiments that could be done to test this (such as all of the animal work).

Please let us know if you have further questions. Good luck!
Pharma
sciencerocks18
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Re: coffee's caffeine effects on parkinson's disease

Post by sciencerocks18 »

Hi Pharma

Thanks for elaborating on the signaling pathway diagrams and offering some suggestions as to the layout of my presentation. However, will my diagram have to be as detailed as the one in the image with numerous proteins/signaling molecules for my project? Do I also have to include many factors that affect parkinson's disease on the outer border of the diagram so along the orange line in the picture you sent me?
I am finishing off my online submission now since I have all my research done. One of the subcategories in the application process is the mentor section. I need to give you credit for all the help that you offered me for this project. So, can you please reply with the following information: your first and last name, e-mail address, phone number, organization, and position. Once again, I would like to appreciate you for your time and efforts!


From
Hareshan
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Re: coffee's caffeine effects on parkinson's disease

Post by PharmaMan »

Hi Hareshan,

No, your diagram will not have to be as detailed as in the example. The example that I sent includes many different pathways, but for your project, I would just focus on the key pathway that you are interested in describing for your project. I would include some factors that can lead to Parkinson's, but not on the signaling diagram. On the signaling diagram, you will be showing how caffeine treatment affects the pathway of interest. Essentially, you can have two different schematics; one can be showing the factors leading to Parkinson's and the major changes that happen (changes in neurotransmitter levels, etc.), and the other can show how caffeine treatment works (signaling pathway diagram).

And you are very welcome. I am glad to be of assistance to you for this project. The experts here, however, are not permitted with sharing contact/identifying information, and we are limited to assisting through the forums. But you can certainly list us at ScienceBuddies as your mentor!

Please let us know if you have any further questions. Best of luck!

-Pharma
sciencerocks18
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Re: coffee's caffeine effects on parkinson's disease

Post by sciencerocks18 »

Hi,

I have completed most of my research. I had also found multiple dopamine signaling in Parkinson's disease pathways. However I do not know where to incorporate the adenosine a2a receptors antagonists, its G-Proteins, and ERK1/2.
I have the url code of the pathway that I was studying below.

http://www.cellsignal.com/common/conten ... hways-park

Will I have to create a totally different signalling pathway or is there some way that I can make minimal modifications to this diagram to explain how my treatment would work at a molecular level?

Once again, I would like to thank you for supporting me and any help that you can offer is greatly appreciated.

From
Hareshan
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Re: coffee's caffeine effects on parkinson's disease

Post by PharmaMan »

Hi Hareshan,

Yes, so I see that this diagram only incorporates a few of the components you are interested in describing. I wouldn't include all of the other mechanisms into your project, only because it isn't your main focus. You could discuss some of the other pathways in an introduction or something similar, but for your project, you are interested in discussing how blocking the A2A receptor with a specific compound (caffeine) works. Therefore, the key pathways you will describe should just be on this pathway, and how the signaling is modulated following the caffeine treatment.

If you have drawing programs, such as CorelDraw or even PowerPoint, you can make a signaling diagram with only the components of interest to you. This is what should be one of your main figures. I'm assuming you're following the same signaling pathway described in the paper listed earlier in this thread?

Best,
Pharma
sciencerocks18
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Re: coffee's caffeine effects on parkinson's disease

Post by sciencerocks18 »

Hi,

I think that I have completed most of my research.
Now I am working on putting it all together on a slide show and then pasting it on a 3 panel board.
I have never done a science fair project in the Health Sciences field and especially a study with no experiments before.
Can you tell me all of the components that I must include in a research study project that would be best applicable for my project?
In addition, can you also explain the difference between pre-synaptic vs. post-synaptic in relation to the dopaminergic neurons and adenosine a2a receptors?

From
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