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Parkinson's Disease

What is it?

 

Parkinson's Disease (PD) is defined as a progressive neurological disorder that affects movement, muscle control, and balance as a result of dopamine (DA) deficiency.

 

 

 

Symptoms

 

Patients diagnosed with PD often experience

key symptoms including:

 

  • Temors

  • Speech difficulty

  • Stiffness or rigidity of muscles

  • Coordination difficutly

  • Digestive problems

 

 

To the Root of it All: Dopamine

 

 

 

Dopamine is a monoamine neurotransmitter developed from tyrosine, one of the major amino acids located within the human body, that assists in transmitting signals within the brain. Without the necessary production of this hightly important chemical, the messages that tell the body how to move are lost or distorted, resulting in the symptoms often seen in a PD patient. Dopamine is produced in the section of the midbrain known as the Substantia Nigra.

[Image Citation] A molecular structure of the dopamine neurotransmitter.

[Image Citation] A real life brain with arrows indicating the dark areas of the substantia nigra.

The Substantia Nigra, located specifically in the portion of the basal ganglia, is in control of the body's voluntary movement and is capable of regulating mood. A healthy Substantia Nigra, as depicted above, contains two areas high in melatonin which allow it to appear "blackish" to the human eye. When healthy, this portion of the brain is able to secrete dopamine which allows the body to move accordingly.

[Image Citation] The colored area in the diagram to the left shows the basal ganglia complex.

When the Substantia Nigra has degraded by nearly 80% - meaning once a significant portion of the nerve cells in this area of the brain die - then the necessary amount of dopamine needed by the body to main voluntary movement is no longer produced. And in this case, those rich areas of melatonin within the Substantia Nigra disappear and a patient is diagnosed with PD.

[Image Citation] A diagram illustrating the Substantia Nigra of a normal person and a person diagnosed with PD.

 

 

The Four Dopaminergic Pathways

 

Within the brain there are four major pathways, also referred to as neural networks, that are able to transmit dopamine.

 

 

 

 

Brain region 2

Brain region 1

Brain region 3

[Image Citation] A diagram illustrating the interconnected neurons that compose the the brain pathways.

  • Nigrostriatal Pathway: The Nigrostriatal Pathway is important in respects to Parkinson's Disease because it is responsible in regulating movement. When a sufficient amount of dopamine is unable to be transmitted from the Substantia Nigra to the Corpus Striatum, the human body will undergo the symptoms of a PD patient.

  • Mesocortical Pathway: The Mesocortical Pathway, though not relatively important to symptoms of PD like the Nigrostriatal Pathway, is responsible for the regulation of behaviors such as emotion and motivation by transmitting dopamine from the Ventral Tegmentum to frontal lobes of the brain.

Mesolimbic and Mesocortical pathways

  • Memory

  • Motivation/emotional response

  • Reward & Desire

  • Addiction

  • Hallucinations & Schizophrenia

Nigrostriatal Pathway

 

  • Motor Control

  • Parkinson's Disease

Tuberoinfundibular Pathway

 

  • Hormonal regulation

  • Maternal behavior

  • Sensory processes

  • Mesolimbic Pathway: The Mesolimbic Pathway, also not relatively important to the symptoms of PD, is responsible for the behaviors relating to motivation, emotion, and memory through the transmission of dopamine from the area of the midbrain to the Limbic System.

  • Tuberoinfundibular Pathway: The Tuberoinfundibular Pathway, like the other two dopaminergic pathways, is not fundamentally important regarding the symptoms of PD, but it responsible in its secretion of hormones through the transmission of dopamine from the Hypothalamus to the Pituitary Gland.

[Image Citation] The four major dopaminergic pathways.

[Image Citation] The four dopaminergic pathways and their responsibilities.

 

Parkinson's Disease Medications

 

Though a person diagnosed with PD cannot be cured completely, their symptoms can be temporarily cured with a series of medications.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

  • Levodopa & Carbidopa: Levodopa, commonly referred to as L-Dopa, is the first medication taken from this duo to treat the symptoms of PD, by replenishing the amount of dopamine lost in the Substantia Nigra. Because dopamine cannot be directly transferred to the selected areas of the brain due to its inabililty to cross the blood barrier to reach the desired location, and due to its nature of breaking down rapidly within the body, its precursor, Levodopa, is taken.

 

 

 

 

[Image Citation] A photograph of Levodopa and Carbidopa.

[Image Citation] An illustration of L-Dopa crossing the blood barrier and being converted to dopamine.

Once L-Dopa has reached the brain and crossed the blood barrier, the dopaminergic enzyme, DOPA decarboxylase, breaks down the medication and converts it into dopamine. From there the important chemical is transported across the Nigrostriatal pathway and used by the body accordingly. Now, Carbidopa, the other medication that works with Levodopa, is needed for L-Dopa to carry out its functions. Carbidopa, known scientifically as a decarboxylase inhibitor, prevents the breakdown of L-Dopa outside of the body before it reaches the brain. By taking Carbidopa, more levodopa is allowed to pass through the Nigrostriatal pathway to be used by the body.

  • Dopamine Agonists: The role of the dopamine agonist is to supply dopamine to the area of a basal ganglia. Dopamine agonists work by mimicking the actions and behaviors of dopamine and stimulating the signalling pathways that belong to these dopaminergic receptors. From here, the drug is accepted into the dopaminergic pathways and allowed to be used by the body accordingly.

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Walking in the footsteps of a person diagnosed with Parkinson's Disease.

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  • Mao-B Inhibitor:

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