Preview of Understanding Parkinson's Disease

The essential cause is not known. Clues are available from studies of the distribution of the disease, that is, who is affected, where and in what circumstances. These show associations that don’t prove a cause, but lead to the investigation of possible causal or contributory factors, which may play a part in causing the illness. It is relatively common – that men and women are equally affected, and that no race is immune. It is not related to any particular job and is clearly a physical disease of the brain, which is not caused by stress, anxiety, emotional or family upsets. Extensive searches for a viral or bacterial cause have proved negative, so the disease is not infectious.

Nerve cells in the brain are affected

In patients with Parkinson’s disease, there is disease or degeneration of the so-called basal ganglia in the deeper grey matter of the brain, particularly of that part known as the substantia nigra.

The substantia nigra, which connects with the striatum (caudate nucleus and globus pallidus), contains black pigmented cells and, in normal individuals, produces a number of chemical transmitters, the most important of which is dopamine. Transmitters are chemicals that transmit, that is, pass on, a message from one cell to the next, either stimulating or inhibiting the function concerned; it is like electricity being the transmitter of sound waves in the radio. Other transmitters include serotonin, somatostatin and noradrenaline. In Parkinson’s disease, the basal ganglia cells produce less dopamine, which is needed to transmit vital messages to other parts of the brain, and to the spinal cord, nerves and muscles.

The basal ganglia, through the action of dopamine, are responsible for planning and controlling automatic movements of the body, such as pointing with a finger, pulling on a sock, writing or walking. If the basal ganglia are not working properly, as in Parkinson’s disease patients, all aspects of movement are impaired, resulting in the characteristic features of the disease – slowness of movement, stiffness and effort required to move a limb and, often, tremor.

Dopamine levels in the brain’s substantia nigra do normally fall with ageing. However, they have to fall to one-fifth of normal values for the symptoms and signs of parkinsonism to emerge.

In Parkinson’s disease, there is degeneration of the substantia nigra which produces the chemical dopamine deep inside the brain.

An important balance

Normally, there is a balance between dopamine and another neurotransmitter – the transmitter of nerve impulses – called acetylcholine. Acetylcholine is present in many areas of the brain and plays a part in normal memory recording and recall. As dopamine is depleted, there is a relative excess of acetylcholine. Thus two of the main groups of drugs used to treat Parkinson’s disease are dopamine drugs (levodopa and its preparations Madopar and Sinemet) and drugs designed to restore the balance by diminishing the acetylcholine – anticholinergics (for example, benzhexol [Artane], orphenadrine [Disipal] and benztropine [Cogentin]).

How do the nerve cells send messages?

The diagram on below shows how the nerve cells or neurons in the basal ganglia release packages of the dopamine, transmit it down its main wire or axon, and how this sprouts into receptors of the next nerve cells and transmits the message and nerve impulse further down the line. You can imagine this process carried out by millions of neurons at the same time, forming a network of activity which puts BT and other telephone networks to shame.

Current ideas about the cause of Parkinson’s disease suggest a predisposition that makes certain people more vulnerable to some (unidentified) environmental toxic agents. Why cells die in the substantia nigra of Parkinson’s disease patients is unknown. This important group of cells shows three changes:

1. Evidence of the release of oxygen compounds by cells which act as a stress that damages cells (oxidative stress), and depletion of a chemical called reduced glutathione.
2. High levels of iron.
3. A deficiency of an essential component of all cells (mitochondrial complex I) that normally controls oxidative reactions; these last involve the release of oxygen compounds which act as stress causing damage to the cells.
4. Which of these is the primary event, causing secondary changes culminating in death of the nigral cells, is not known. In people with Lewy bodies in their brains but before the development of symptoms of parkinsonism, the substantia nigra shows a comparable loss of reduced glutathione and, possibly, a reduction of complex I activity. Lewy bodies are small areas in nerve cells (inclusions) present in practically every case. They are pink acidophilic (acid-loving) blobs, and show a central core with a peripheral halo. As they may be signs of very early disease, before definite signs emerge, these various abnormalities provide a new focus for the development of future treatments.

Various parts of the nervous system combine to generate movement. Nerve impulses start in the cortex, pass through the basal ganglia, brain stem and spinal cord, and finally pass through the peripheral nerves which actually control muscles.

Receptors are important

The receptors are most important. Some drugs can block the receptors, and if they are taken for a long period they block the passage of dopamine in the nerve cells and their connecting network of axons. The nerve impulses so essential for normal movements are therefore reduced. This is the basis of the drug-induced parkinsonism.

Ageing and heredity

Although Parkinson’s disease is not caused by the normal ageing process that affects all our brains, just as it does other organs, the incidence of the disease does increase as we get older. The possible role of a genetic abnormality and of hereditary transmission is one of the fertile areas for present and future research. A weak link has been found between Parkinson’s disease and Alzheimer’s disease, but genetic studies have ruled out any important connection. Nor do the results support any role for genetic factors in the dementia sometimes associated with Parkinson’s disease. A family history is obtained in five to ten per cent of patients, but studies on twins suggest that hereditary factors are relatively unimportant. It may be that affected relatives share some environmental agent or are genetically vulnerable to it. What this environmental factor might be, we do not know.

Dopamine is released from storage granules in the nerve cell, and travels down the axon across the synaptic knob to dopamine receptors at the next nerve cell.

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