[olsen]

Gladstone scientist finds new target for treating symptoms of Parkinson's disease

posted on: september 8, 2011 - 4:30am

SAN FRANCISCO, CA—September 8, 2011— A scientist at the Gladstone Institutes has identified how the lack of a brain chemical known as dopamine can rewire the interaction between two groups of brain cells and lead to symptoms of Parkinson's disease. ...
(the researcher)identifies how the loss of dopamine alters the wiring of a small group of brain cells, kicking off a chain of events that eventually leads to difficulties controlling movement—...



Normally, two types of brain cells called medium spiny neurons, or MSNs, work together to coordinate body movements, with one type acting like a gas pedal and the other as a brake. It has been thought that a reduction in dopamine, an important chemical in the brain, throws off the balance between the two opposing MSN forces, leading to problems with movement. ... Dr. Kreitzer artificially removed dopamine from the brains of laboratory mice and monitored the specific changes in the brain that followed.

Just as happens in humans, the mice without dopamine began to experience the motor symptoms of Parkinson's... But Dr. Kreitzer found that decreased dopamine levels didn't just throw off the balance between the two types of MSNs, as was already known, but they also changed the interaction between MSNs and another group of neurons called fast-spiking neurons, or FSNs.

Dr. Kreitzer's experiments showed that under normal circumstances, FSNs connect to both types of MSNs in a similar way. But without dopamine, the signaling between the FSN circuits gets rewired and the neurons begin to target one type of MSN over the other. Dr. Kreitzer used computer simulations to show that this small shift disrupts the timing of MSN activity, which is key to normal movement. Ultimately, this rewiring may be an important factor in the development of Parkinson's motor problems.

http://www.sciencecodex.com/gladston...insons_disease

[Conductor71]

Interesting, but does not explain the many manifestations of Parkinsonian symptoms; there are many cases where there is no loss of dopamine but very real loss of movement. For example, I have come across case studies on PubMed where people present with signs of PD and seem to decline pretty rapidly and upon CAT scan are found to have a blod clot deep in the brain and responsive to levodopa. When the clot is treated early enough all PD signs vanish. The medical term is subdural hematoma.

I am so jaded at this point that whenever I see the words "cause" or "development" and especially "leading to new treatment targets" I want to run screaming. I file iti in my head as cause #231 of PD. How in the world will this treatment happen without them even being able to measure that we have a loss of dopamine in the first place. They assume we all have the same thing going on in our brains when they don't really have a clue. See Harley's post on the DatScan.

Olsen, don't take this personally, any post that informs or provokes discussion is good, but I see this as an example of the problem with the absence of goal directed research...it might be relevant in the future but until they can actually figure out basic things like measuring our dopamine levels as a baseline and measure neuronal loss at regular intervals (say once a year) thereafter, then I don't see how intervening at this invasive a level would be safe let alone beneficial. I'd rather see research directed at how to develop what we need to diagnose more accurately.

Laura

[lindylanka]

I believe that this research could actually point to some of the reasons WHY we are different. The fundamental unbalancing that is discussed and the 'rewiring' aspects too have a kind of logic to them. For instance it could explain why tremor is the major visible sign for some of us, and rigidity for others. I have long had questions about this, why are some of us shakers, and others stiff, they are like the opposite ends, and functioning well is the fulcrum, so what shifts things one way or the other? It also seems to tie in with some of the neurotransmitter balance stuff too....... like how for some of us anticholinergics can help (less dopamine means the dopamine/acetylcholine balance goes out of whack, address this and you get symptomatic improvement). More than this, it could explain what tremor is all about. My reading of it anyway. And the rewiring might explain our loss of automaticity....... Like Laura I don't think this will lead to new treatments, but perhaps it will contribute to looking at PD in a fresh way, not so based on ldopa (small picture) only. What I would like to see is the better thinking integrated into a bigger picture of what is going on. Then that sense of being a whisker away from normality that we sometimes feel might actually start to translate into the possibility of treatments for all of us, not just the ones with 'classic' pd.

Thanks for posting about this.

[SaraRiggare]

Read Jon Stamfords commentary on the recent findings on Parkinson's Movement's website **. Also please feel free to ask questions or comment yourself there.

Sara

[olsen]

Hi Laura, no worries; I do not take it personally. And am in concert with your expressed opinions about the newest "breakthrough finding" and "new target". Still feel the need to keep reading and searching, hoping something will hit one of us as an "ahaaa" moment and result in something positive. I even subscribe to "Ode" magazine--and just noted on the preface it is for "intelligent optimists". Sheesh. Just think that is funny. madelyn

Originally Posted by Conductor71

Interesting, but does not explain the many manifestations of Parkinsonian symptoms; there are many cases where there is no loss of dopamine but very real loss of movement. For example, I have come across case studies on PubMed where people present with signs of PD and seem to decline pretty rapidly and upon CAT scan are found to have a blod clot deep in the brain and responsive to levodopa. When the clot is treated early enough all PD signs vanish. The medical term is subdural hematoma.

I am so jaded at this point that whenever I see the words "cause" or "development" and especially "leading to new treatment targets" I want to run screaming. I file iti in my head as cause #231 of PD. How in the world will this treatment happen without them even being able to measure that we have a loss of dopamine in the first place. They assume we all have the same thing going on in our brains when they don't really have a clue. See Harley's post on the DatScan.

Olsen, don't take this personally, any post that informs or provokes discussion is good, but I see this as an example of the problem with the absence of goal directed research...it might be relevant in the future but until they can actually figure out basic things like measuring our dopamine levels as a baseline and measure neuronal loss at regular intervals (say once a year) thereafter, then I don't see how intervening at this invasive a level would be safe let alone beneficial. I'd rather see research directed at how to develop what we need to diagnose more accurately.

Laura

[olsen]

http://www.parkinsonsmovement.com/