Parkinson’s disease

LI: to understand the causes, diagnosis and treatment of Parkinson’s disease. Success criteria: Describe the changes in the brain caused by Parkinson’s disease. Identify the four major symptoms. Describe the neuroimaging technique used to diagnose Parkinson’s disease. Describe three treatments for Parkinson’s disease. Describe two studies that have assisted scientists in furthering their understanding of 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. Video: Michael J Fox

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.

Another treatment offer is Deep Brain Stimulation. Deep Brain Stimulation (DBS): a surgical procedure that involves the implantation of an electrode into the brain so electrical impulses can be delivered to specific parts of the brain to activate them. Video: DBS

When the electrical impulses stimulated the neurons that control movement, it blocked the signals causing the tremors, alleviating some of the symptoms of Parkinson’s disease. DBS is usually used in conjunction with drugs. DBS does not halt the progression of the disease.

Research using animal models In 1957, Arvid Carlsson demonstrated that dopamine was a neurotransmitter in the brain and that deficiencies in dopamine led to movement problems. Carlsson used rabbits as his model. He gave them a drug that removed dopamine from their brain and observed their behaviour.

The rabbits went into a physical trance and did not respond to stimuli (no movement). After giving the rabbits Levodopa, the rabbits movements were restored. He won a Nobel Prize for his work in 2000.

Monkeys were the animal models used for the first tests of DBS Monkeys were the animal models used for the first tests of DBS. They replicated the death of cells in the basal ganglia to replicate Parkinson’s disease (drugs to halt production of dopamine).   They realised that the cell death in the basal ganglia led to overactivity in movement areas of the brain and that DBS would alleviate this overactivity.

Other research Genetic modification work is now being performed using mice and pigs to try to understand the cause of Parkinson’s. Stem cell research is also another area that has made some progress in alleviating symptoms of Parkinson’s in rats.

Activities Student Activity Manual: 4.6, 4.7