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PD and the Brain

To best understand the effects Parkinson's has on the brain, it is important to understand how the brain works. John M. Vine, author of a Parkinson's Primer breaks this down in his book for clarity and understanding. Below is an insert:

The Brain

Parkinson's is, at least in part, a disease of the human brain. The brain is the most complex part of the human body. In fact, the human brain is probably the most complex thing on Earth. The human brain is far more complex and powerful than the most advanced computer. Scientists are now only beginning to understand how the brain works.

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  • Neurons: The primary unit of the brain is the brain cell or neuron. The brain consists of roughly three pounds of neurons floating in four to five ounces of fluid inside the skill. It is estimated that a normal human brain contains approximately 86 billion neurons. Whatever the precise number of neurons, that figure is large by almost any standard -- much larger, in fact, than the number of people currently living on Earth (about 7.3 billion).

  • Neurotransmitters: Neurons send signals to other neurons by releasing (or secreting) chemicals called neurotransmitters. The brain uses neurotransmitters to instruct the heart to beat, the lungs to breathe, and the stomach to digest. Neurotransmitters can affect mood, sleep, and concentration. Current estimates are that the brain has more than 100 neurotransmitters, each with a specific function or functions. Some neurotransmitters are excitatory; others are inhibitory; and still others are both excitatory and inhibitory. Excitatory neurotransmitters stimulate the brain. Inhibitory transmitters calm the brain and help create balance. Inhibitory neurotransmitters are easily depleted when excitatory neurotransmitters are overactive.

  • Neuronal Networks: Neurons communicate with each other through highly structured neuronal networks. Each neuron receives signals from, and sends signals to, other neurons in complex brain circuits. It is estimated that one neuron can receive messages from and send signals to, up to 10,000 other neurons. Neurons are separated from other neurons by small gaps, called synapses. When a neurotransmitter is released by one neuron (call it "neuron #1), the neurotransmitter leaves what is called the axon terminal of Neuron #1, travels across a synapse to another neuron (Neuron #2), and attaches itself to a receptor on Neuron #2. An electrical signal is then activated or inhibited in Neuron #2. If the electrical signal reaches the end of Neuron #2, Neuron #2 itself releases a neurotransmitter, which travels across a synapse and attaches itself to yet another neuron. The cycle begins again.

Parkinson's Effects on the Brain

Parkinson's disease reduces the levels of three of the brain's neurotransmitters: norepinephrine, serotonin, and dopamine.

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Norepinephrine is an excitatory neurotransmitter. It is responsible for stimulatory processes in the body. It is the principal chemical messenger of the sympathetic nervous system, the part of the nervous system that controls many of the body's automatic body functions, such as pulse and blood pressure. Norepinephrine also helps to control mental focus and emotional stability.

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Serotonin is an inhibitory neurotransmitter; it does not stimulate the brain. It regulates appetite, sleep, memory, learning, mood and muscle contraction, among other things. Adequate amounts of serotonin are required for a mood to be stable and to balance any excessive excitatory neurotransmitter firing in the brain.

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Dopamine has both excitatory and inhibitory characteristics. Dopamine performs important functions in the regulation of body movements, memory, cognition, mental focus, sleep, motivation and mood. A dopamine deficiency may cause the body's movements to become delayed and uncoordinated. By contrast, an excess of dopamine may cause the body to make unnecessary movements.

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Parkinson's symptoms develop when approximately 60% to 80% of the dopamine in the brain has been depleted. The loss of dopamine interferes with the individual's ability to control his or her movements. In addition, a loss of dopamine may impair the brain's capacity to process and remember information and to concentrate. The loss of dopamine also may alter the individual's mood. 

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Changes in the brain's neurochemistry resulting from declining levels of norepinephrine, serotonin, and dopamine - together with the stress of a chronic disease -- may help to explain why a significant percentage (perhaps 40%-50%) of Parkinson's patients experience clinical depression at some point during the course of the disease.

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  • The Substantia Nigra: "Substantia nigra" is Latin for "dark substance." The substantia nigra is a crescent-shaped, darkly pigmented mass, located in the mid-brain region, at the top of the brain stem. Neurons in the substantia nigra produce dopamine. Parkinson's disease causes dopamine-producing neurons in the substantia nigra to die. A dopamine deficiency in the substantia nigra leads to Parkinson's movement symptoms.

  • Lewy Bodies: The brain cells of deceased Parkinson's patients contain microscopic clumps of protein, known as Lewy bodies. The Lewy Bodies can be found in particular areas of decreased Parkinson's patients' brains, including the substantia nigra.

  • Alpha-synuclein: The primary component of a Lewy body is a protein called alpha-synuclein. Although alpha-synuclein function in healthy cells is uncertain, there is considerable evidence suggesting that it plays a key role in the development of Parkinson's disease. Ordinarily,  alpha-synuclein's readily dissolves in cell fluids. However, under certain conditions, it becomes insoluble and tends to aggregate and accumulate in clumps. The accumulation of the insoluble form of alpha-synuclein may compromise a cell's capacity to dispose of additional alpha-synuclein. The resulting build-up of alpha-synuclein may be toxic to brain cells and cause neuron dysfunction. Alpha-synuclein pathology has also been discovered, outside the body systems traditionally associated with Parkinson's, offering support for the emerging theory that Parkinson's affects many areas beyond the substantia nigra and extends beyond the central nervous system itself. In fact, Parkinson's earliest symptoms include constipation and other gastrointestinal problems. There is even evidence suggesting that Parkinson's appears in intestinal nerve cells before it appears in the brain.

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Source:

Vine, John M. A Parkinson's Primer: An Indispensable Guide to Parkinson's Disease for Patients and Their Families. Why Parkinson's?. Pages 16-18. Paul Dry Books. 2017.

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