Parkinson’s Disease: Studies Identify Causes and Reasons for Hope

Parkinson’s disease is most often the result of a complex interplay between genetic and environmental factors, which include exposure to neurotoxic chemicals, head trauma, lack of exercise, diet, gut dysbiosis, and chronic stress.

While there is no cure for Parkinson’s disease, there are documented cases of improvement and recovery. Recovery in these cases is defined mainly by the elimination of motor symptoms. Motor symptoms begin when dopamine levels and neuron loss reach a critically low threshold. I’ll explain how that works in this post. When people are able to boost their dopamine levels and/or restore enough dopaminergic neurons that they can get past this threshold, their motor symptoms can go away.

In this post I’ll discuss why motor symptoms occur, research on neurogenesis in the substantia nigra of Parkinson’s patients, how exercise (especially forced exercise) and stress reduction reduce motor symptoms, and stories of recovery from Parkinson’s disease. As you will learn, reducing and potentially eliminating motor symptoms—and even restoring a sense of smell—is a realistic goal that Parkinson’s patients are already pursuing.

How Motor Symptoms Occur in Parkinson’s disease

The motor symptoms of Parkinson’s disease typically appear years after the disease process has begun—often 20 or more years after. (1) It’s estimated that motor symptoms appear when approximately 30 percent (2) to 60 percent of dopaminergic (dopamine-producing) neurons in the substantia nigra are lost. (3)

Studies show varied results when it comes to the actual percentage of substantia nigra neuron loss necessary to produce motor symptoms, and it’s safe to say that the exact percentage is different from person to person. Regardless of the percentage, it is understood that when dopamine levels decrease to a critical threshold, tremors or other motor symptoms may be felt—sometimes suddenly. For many people, this is the first noticeable sign of the disease.

Dopaminergic neurons in the substantia nigra send dopamine into two basal ganglia motor loops, referred to as the direct pathway of movement and the indirect pathway of movement. Dopamine regulates motor activity by acting on dopamine receptors, of which there are two types: D1-like receptors are present in the direct pathway, and D2-like receptors are present in the indirect pathway (if you read more about this topic, you’ll hear about these receptors).

The direct pathway allows us to move in ways that we want to; activation of the direct pathway increases ease of movement and of initiating movement. In contrast, the indirect pathway allows us to suppress the unwanted movement.

The direct pathway is referred to as the “Go” pathway, while the indirect pathway is referred to as the “NoGo” pathway. When the Go pathway is activated, we move easily; when the NoGo pathway is activated, movement is suppressed.

Low or fluctuating levels of dopamine, which occur in Parkinson’s disease as dopaminergic neurons die off, weaken the direct pathway and strengthen the indirect pathway. When dopamine levels fall to a critical threshold, tremors or other motor symptoms may occur, sometimes suddenly, as the indirect pathway is activated.

Research on Neurogenesis

Parkinson’s disease is a degenerative neurological condition in which dopaminergic (dopamine-producing) neurons in a part of the brain called the substantia nigra die off. Other parts of the brain suffer neurodegeneration as well, causing some of the non-motor symptoms of Parkinson’s. I’ll now discuss promising research about neurogenesis (production of new neurons) as it applies to Parkinson’s disease.

In 2003, scientists in Sweden demonstrated that neurogenesis occurs in the substantia nigra of adult mice. (4) Their research showed that the type of dopaminergic neurons lost in Parkinson’s disease is actually regenerated throughout life. While the rate of neurogenesis in the substantia nigra is slower than in the hippocampus, if the rate of neural turnover is constant, the entire population of dopaminergic neurons in the substantia nigra could be replaced during the lifespan of a mouse. The study showed that not only does neurogenesis in the substantia nigra occur, but the newborn neurons are then integrated into neural circuits.

The discoveries of this study imply that “disturbances in the finely tuned equilibrium of cell genesis and cell death could result in neurodegenerative disorders.” The researchers suggest that Parkinson’s disease could in some cases be caused by decreased neurogenesis rather than increased cell death. Another explanation they suggest is that neurogenesis in Parkinson’s patients can’t keep up with the increased rate of cell death caused by Lewy bodies.

Stem Cells Offer Hope

In 2016, researchers at Boise State University in Idaho discovered that dopaminergic neurons are replenished in adult mouse models of Parkinson’s disease. The researchers created a chronic, systemic inflammatory state in mice’s brains to simulate that which occurs in Parkinson’s disease. (5) Their results indicate that inflammation may inhibit neurogenesis in the substantia nigra, leading to or contributing to the net loss of neurons in Parkinson’s disease. The researchers note that neurogenesis has been difficult to prove due to limitations of current cell lineage tracing methods, and they were able to demonstrate neurogenesis of nigral neurons using a new tracing model that they developed.

In 2011, neuroscientists in the Netherlands studied the brains of 25 people: 10 with Parkinson’s disease, 10 healthy controls, and 5 with Lewy body disease (the presence of Lewy bodies, but no clinical symptoms of Parkinson’s disease). The researchers found neural stem cells in the subventricular zone of every donor, (6) with no significant differences in number between the three groups. They cultured neural stem cells from Parkinson’s patients and confirmed that the cells were viable. While this was a small study, having proof that viable neural stem cells are produced in the brains of Parkinson’s patients is extremely encouraging.

An article in the Journal of Experimental Neuroscience states (7): “To compensate the degenerative rate of DAergic neurons, we have only 2 choices, either enhance the formation of newborn neurons and endogenous regenerative capacity or reduce the death rate of existing neurons.” Many scientists are pursuing the first route—exploring ways to enhance our natural process of producing neural stem cells to replace the dopaminergic neurons that are lost in Parkinson’s disease.

In 2012, researchers in South Korea injected human stem cells into mice with Parkinson’s disease. The stem cells increased neurogenesis (8) in the subventricular zone and the substantia nigra, which led to an increase in the number of neural precursor cells that turned into dopaminergic neurons in the substantia nigra. The researchers suggest that this approach of enhancing endogenous neurogenesis to repair the damaged Parkinson’s brain could have a significant impact on future strategies.

A Novel Approach to Parkinson’s Disease

However, scientists in the Netherlands (9) and Australia (10) favor non-invasive approaches. They caution that transplanting neural stem cells has both ethical and immunological challenges. When doing stem cell transplants, a donor is necessary, and the patient’s immune system must be suppressed in order to prevent rejection. These scientists prefer non-invasive treatment approaches that stimulate neurogenesis and mobilize endogenous neural stem cells—those that are naturally produced in the brain—to survive, migrate, and differentiate into dopaminergic neurons in the substantia nigra.

One such approach is being explored by neuroscientists at the Karolinska Institute in Sweden. By injecting transcription factors (proteins that regulate genes) into mice with Parkinson’s, they can turn astrocytes (an abundant type of brain cell that provides support and maintains homeostasis) into dopaminergic neurons. Five weeks after receiving treatment, the mice with Parkinson’s were walking normally. This “direct reprogramming of brain cells has the potential to become a novel therapeutic approach for Parkinson’s.”

One of the study authors notes that the reprogrammed cells would probably be damaged by whatever caused Parkinson’s in the first place. In cell transplants for other health conditions, the disease tends to catch up with transplanted cells in 15-20 years. Treatments to enhance endogenous neurogenesis will likely buy Parkinson’s patients important time, but they may need to be repeated.

Until and even after these treatments become approved for human use, it is extremely important for Parkinson’s patients to understand how to enhance neurogenesis naturally. Exercise and stress reduction are two of the best ways to encourage neural stem cells to survive, migrate, and differentiate into the type of neurons that the brain needs. Parkinson’s patients are already using exercise and stress reduction to repair their damaged brains, and the result is a reduction or elimination of motor symptoms, and even restoration of the sense of smell.