“The effects of chronic changes to the functioning of the nervous system due to interference to neurotransmitter function, illustrated by the role of Dopamine in Parkinson’s disease.”

Parkinson’s Disease Parkinson’s disease: a CNS neurodegenerative disorder characterised by both motor and non-motor symptoms. Neurodegenerative disease: a disease that gradually and progressively kills nerve cells (neurons) and results in nervous system dysfunction and permanent loss of ability.

Causes of Parkinson’s Disease The cause (trigger) of Parkinson’s disease is still not known and there is no evidence that it has a genetic basis. However, researchers do know how it effects the brain.

1. Neurons start to degenerate (die) in the substantia nigra in the midbrain. 2. Neurons in the substantia nigra produce the neurotransmitter dopamine. When this area is damaged, the levels of dopamine are reduced.

3. Less dopamine means less motor activity, as dopamine is the neurotransmitter responsible for controlling voluntary motor movements. 4. The substantia nigra releases dopamine and sends the messages about motor movements to the basal ganglia and then the motor cortex, in the frontal lobe.

5. With lower levels of dopamine, the messages travelling to the motor cortex to control voluntary movements are slower and fewer. This causes impairments in the control of voluntary movements and some of the major symptoms of Parkinson’s disease.

Symptoms Motor symptoms only appear after substantial neuronal death in the substantia nigra. Approximately 60% of the neurons need to die before symptoms start occurring.

The four main symptoms for diagnosis: 1. Tremor or shaking (most common) that usually starts in one hand 2. Muscle rigidity, stiffness of the muscles which seem unable to relax

3. Bradykinesia (slowness of movement and gradual loss of spontaneous movement) 4. Postural instability, balance problems and gait (walking) disturbances

Diagnosis PET imaging: PET scans show the dopamine producing areas of the brain. It makes it possible to assess changes in the activity and function of the brain PET imaging diagnoses Parkinson’s by injecting a patient with the drug, 18F-DOPA. This drug is similar to dopamine. It shows the deterioration of the pathways in the substantia nigra, if a person has Parkinson’s.

Treatment There are two drugs used to treat Parkinson’s disease by increasing the level of dopamine in the brain. - Levodopa (L-Dopa) can cross the blood-brain barrier and be converted into dopamine by the brain. - Dopamine agonists stimulate the dopamine receptors in the brain, mimicking the effect of dopamine in the brain.

Both drugs can alleviate the motor symptoms of Parkinson’s, but are not a cure. The disease continues to progress until the drugs do not work anymore, or cause side effects such as dyskinesia, which are just as bad as the disease. Dyskinesia: abnormal involuntary muscle movements. 5-10 years is the maximum benefit of medication.