Exercise and pharmacological treatment: a synergy in Parkinson's disease | Giselle Petzinger
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Dopamine loss disrupts brain circuitry that may be fundamental in Parkinson's disease. Dopamine replacement drugs, such as levodopa, alleviate motor symptoms of the disease, but people often experience side effects over time. In clinical reports, those who decline dopamine replacement often experience excessive fatigue rendering them unable to exercise and gain its benefits. In this clip, Dr. Giselle Petzinger discusses how no evidence exists that lifestyle factors, such as diet and exercise, can cure Parkinson's disease or obviate the need for dopamine replacement.
[Giselle]: One of the things I have to say though, that I always try to make clear to people is, one, there is no data that it stops disease. So that's the one thing. It's never shown it cures Parkinson's. And two, I also want to make sure that we inform patients that it's not a replacement for dopamine. And the reason that's important is because we also had some experience with individuals who were frightened of dopamine, and I know there's a lot of literature out there that can be very frightening for people, but the idea that they weren't taking dopamine, all they wanted to do was exercise. And what we noticed is that those people really struggled. I mean, they really were not able to get the most out of practice. They have a lot of fatigability when they tried to exercise. And so, the point was they didn't really get the benefits of exercise because they couldn't do it, right? And so, the other part of the equation is there's a reason for dopamine, right? And so, dopamine has a role for synaptic plasticity. Obviously, practice is as important, but dopamine enables plasticity.
[Rhonda]: Can you talk about little bit about... So there's the standard of care treatment right now, is levodopa, carbidopa, right?
[Giselle]: Right. So dopamine replacement, because Parkinson's disease, as I said is, causes, obviously dopamine depletion with circuit changes, but the dopamine depletion also, it's driving some of this loss, this loss of connections. We need dopamine back because dopamine is what enables synapses to form as well along with practice and it also alleviates the symptoms themselves. So treating with L-DOPA will help a lot of the symptoms of slowness and stiffness that will allow you to get the most out of practice. I can move better. I can move more accurate when I can, you know, I'm not feeling a slower stiff. So, you know, again, I think of the L-DOPA, which is what we give, Carbidopa/levodopa.
[Rhonda]: L-DOPA gets converted in a dopamine, so L-DOPA across the...
[Giselle]: Yeah. So L-DOPA is a pro-drug that I ingest with carbidopa. Carbidopa blocks the peripheral metabolism L-DOPA so it doesn't break down in the blood or make me sick.
[Rhonda]: The carbidopa prevents L-DOPA from becoming dopamine before it gets into the brain. Is that right?
[Giselle]: That's correct. But the idea there is once L-DOPA makes into the brain, it gets converted in the brain in those remaining cells to dopamine, and that is now targeting those circuits that I mentioned, the automatic circuits, right? And that's what allowing it to work more efficiently. And then the idea is with adding exercise, it may also drive repair.
[Rhonda]: So you're saying that exercise is not a replacement for the L-DOPA or carbidopa, but it's in combination, you know, because you obviously still need the dopamine. And I think that the L-DOPA and the carbidopa itself doesn't actually slow disease progression, but it does help treat symptoms, but that's...after a certain time, doesn't some of those become refractory doesn't, is it...
[Giselle]: I would say there are several points. One is that it, you know, because those cells are not storing it as well, you know, you're having to dose more frequently. So that's a cell dysfunction problem. And then secondarily, there were other circuits, cognitive circuits, as an example that are getting affected. And we know cognition plays a big role in my ability to move safely through space. And so, that's going to be a big contributor. And L-DOPA does not do as much. It's not as a factor for cognitive function. It has a role there, but it's one of many different chemicals. Acetylcholine being another one, serotonin, norepinephrine being other ones.
[Rhonda]: These things are also modulated by exercise. And there have been meta-analyses that have been done looking at various types of exercise and their effect on cognitive function, executive function, global cognitive function, memory, and those things can be improved by high intense.
[Giselle]: Right. And aging field I'd say is a little further ahead of us in terms of their data. Probably the strongest data in the aging field right now.
[Rhonda]: Absolutely. It is. But there are some with Parkinson's patients that they have looked at and so, it certainly is affecting cognition as well
A neurotransmitter best known for its role in motor, motivation, and pleasure control. Dopamine also functions as a paracrine (cell-to-cell) hormone in other parts of the body. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Some evidence suggests that dopamine may also be involved in pain modulation.
Important for the endocrine enhancing properties of exercise. Exerkines are exercise-induced hormonal-like factors which mediate the systemic benefits of exercise through autocrine, paracrine, and/or endocrine properties.[1]
- ^ Helge, Jørn Wulff; Moritz, Thomas; Morville, Thomas; Clemmensen, Christoffer; Dela, Flemming (2020). Plasma Metabolome Profiling Of Resistance Exercise And Endurance Exercise In Humans Cell Reports 33, 13.
An essential mineral present in many foods. Iron participates in many physiological functions and is a critical component of hemoglobin. Iron deficiency can cause anemia, fatigue, shortness of breath, and heart arrhythmias.
A dopamine-replacement drug used to treat Parkinson's disease. Levodopa, also known as L-Dopa (or L-DOPA), enters the brain via the blood-brain barrier and undergoes conversion to dopamine. The subsequent increase in brain concentrations of dopamine improves nerve signal conduction and alleviates movement disorders. Levodopa is commonly taken orally along with carbidopa, a drug that prevents the breakdown of levodopa before it reaches the brain.
The thousands of biochemical processes that run all of the various cellular processes that produce energy. Since energy generation is so fundamental to all other processes, in some cases the word metabolism may refer more broadly to the sum of all chemical reactions in the cell.
A substance produced in the brain. Norepinephrine acts as a hormone and neurotransmitter and is best known for its role in the body’s “fight or flight” response to stress. Its role as a neurotransmitter has been exploited as a molecular target for a class of drugs known as norepinephrine reuptake inhibitors, which were developed for the purpose of treating disorders ranging from ADHD to narcolepsy and depression. Norepinephrine also plays a role in converting white adipose tissue into brown adipose tissue via an uncoupling protein 1 (UCP-1) mediated mechanism.
A neurodegenerative disorder that affects the central nervous system. Parkinson’s disease is caused by destruction of nerve cells in the part of the brain called the substantia nigra. It typically manifests later in life and is characterized by tremors and a shuffling gait.
An antibody that plays key roles in immunity. Secretory IgA is the most abundant antibody in the mucosal immune system, accounting for nearly 20 percent of serum immunoglobulin. It is crucial in protecting the intestinal epithelium from toxins and pathogenic microorganisms.
A small molecule that functions as both a neurotransmitter and a hormone. Serotonin is produced in the brain and gut and facilitates the bidirectional communication between the two. It regulates many physiological functions, including sleep, appetite, mood, thermoregulation, and others. Many antidepressants are selective serotonin reuptake inhibitors (SSRIs), which work by preventing the reabsorption of serotonin, thereby increasing extracellular levels of the hormone.
The junction between one neuron and another or a gland or muscle cell. Synapses are critical elements in the transmission of nerve signals. Their formation is necessary for the establishment and maintenance of the brain’s neuronal network and the precision of its circuitry.
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