The Scicurious Brain

http://blogs.scientificamerican.com/...than-dopamine/



A colleague handed me this paper, not just as an interesting aspect of Parkinson’s...
Politis et al. “Serotonin Neuron Loss and Nonmotor Symptoms Continue in Parkinson’s Patients Treated with Dopamine Grafts” Sci Trans Med, 2012.



... when most people think of potential causes for Parkinson’s, they think of a deficit in dopamine,...again, it’s not just dopamine in the substantia nigra, there are other systems involved and differences in signaling that also play a role as the disease progresses.

But what most people are interested in repairing first is the highly debilitating motor deficit. Treatment has focused very heavily on restoring dopamine and motor function. For example, the first line treatment is Levadopa, or L-DOPA...



But this doesn’t work forever. ... So we are constantly trying to find new treatments to restore function.

One of these new treatments is actually one using stem cells. You can insert a graft of fetal stem cells which express dopamine into the striatum of the brain. When these grafts work (unfortunately, in a lot of cases they do not work, get rejected, or produce bad motor symptoms on their own), they can restore dopamine function to normal levels....

But are these patients WELL? The motor symptoms are better, but what about other aspects? The authors of this study looked at four of the successful stem cell treated patients to see how their symptoms in motor and nonmotor areas compared to controls and other Parkinson’s patients.

What they found was that in motor symptoms, the patients were definitely improved, all of them no longer required medication. Not only that, their measures of dopamine (as measured by positron emission tomography using radiolabeling of l-dopa to look at amino acid decorboxylase, which gives an indirect measure of dopamine) were comparable to controls...


..PET scans[showed]... that the dopaminergic function measure looks completely normal in comparison. The patients also scored very well on all measures of motor function.

…but they weren’t WELL. When the authors looked at measures of the other symptoms, they found that all the patients showed issues, with bowel or sexual dysfunction, mood problems and hallucinations, or sleep issues. And it couldn’t be the dopamine, because dopamine function was restored to normal.

No, it’s not the dopamine, but it could be the serotonin.



While measures of dopamine were normal, measures of serotonin in the stem cell receiving patients were lower even than in untreated patients.



And the decreases in serotonin function extended all over the brain. Norepinephrine function, however, was normal.

The serotonin here kind of makes sense... And Parkinson’s does progress to the serotonin symptom and destroy the serotonin cells in the raphe.

But what this tells us is that it is no longer enough to target the dopamine related symptoms of Parkinson’s alone. It’s a start, but it’s not the best treatment. The authors propose doing multiple grafts of dopamine and serotonin cells, and I think for less severe symptoms there might be reason to combine L-DOPA with an SSRI or something else to increase serotonin function while possible. Clearly, more studies need to be done on how to help these nonmotor symptoms of Parkinson’s. Because restored motor activity is wonderful and incredibly important, but it doesn’t necessary mean a cure.

Politis M, Wu K, Loane C, Quinn NP, Brooks DJ, Oertel WH, Björklund A, Lindvall O, & Piccini P (2012). Serotonin neuron loss and nonmotor symptoms continue in Parkinson’s patients treated with dopamine grafts. Science translational medicine, 4 (128) PMID: 22491951