Parkinson's is much more than dopamine

and much more than motor symptoms.

A colleague handed me this paper, not just as an interesting aspect of Parkinsons, but as somewhat supportive paper for the role of serotonin in depression. I have said before that I think the serotonin theory of depression (as depicted in Zoloft commercials) is probably wrong, but my views are actually a bit more nuanced than that. The serotonin theory is probably wrong, but not because it is wrong, rather, it is oversimplified. I think that low serotonin levels on their own probably dont cause depression, but it looks like there may still be a role for serotonin in depressive symptoms, and this paper seems to agree. Science, its always more complicated than you think at first.

Politis et al. Serotonin Neuron Loss and Nonmotor Symptoms Continue in Parkinsons Patients Treated with Dopamine Grafts Sci Trans Med, 2012.

Parkinsons is something that no one wants to get. Its a degenerative disorder of the nervous system, which results in a wide variety of symptoms. Most people think of Parkinsons and picture a shuffling gait, severe hand tremor, slowness of movement and rigidity. But there are other symptoms as well, include depression, hallucinations, fatigue, sleep disturbances, and cognitive deficits as the disease progresses.

And when most people think of potential causes for Parkinsons, they think of a deficit in dopamine, the neurotransmitter that I usually think of with regard to reward and reinforcement, but which is extremely important in motor systems as well. In Parkinsons patients, you see a striking loss of dopamine neurons in motor areas like the substantia nigra (its easy to see because the melanin in the substantia nigra, which is latin for black substance dyes the cells black, and when those cells die, the stubstantia nigra becomes a lot less substantia and nigra). But again, its 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, a precursor to dopamine which the brain can then use to make dopamine, and which can restore motor function beautifully:

(I have to say the perky music in this video is really pretty horrid, but the effect of the L-DOPA is very visible)

But this doesnt work forever. Eventually the brain stops responding to dopamine supplementation. Then treatments move to brain stimulation or other methods, many of which also eventually fail. 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. The patients can move again, walk again, function normally, and the effects can persist for over a decade (at least, they have persisted for over a decade so far).

Originally posted here:
Parkinson's is much more than dopamine