Parkinson's disease: loss of dopaminergic neurons
In Parkinson's disease, dopamine-producing neurons of the substantia nigra pars compacta (a cell group in the brain stem) die, so the brain circuits that regulate movement receive less dopamine.
Remember
The slowness, stiffness and shake at rest of Parkinson's disease come from losing dopamine-producing neurons in the substantia nigra pars compacta, which leaves the brain's movement circuits short of dopamine; symptoms usually appear once about half of those neurons have been lost.
Parkinson's disease is a progressive neurodegenerative disease in which nerve cells die. The cells that go are the dopamine-producing neurons of the substantia nigra pars compacta, a pigmented group of cells in the midbrain (the upper part of the brainstem).
These cells send axons to the striatum, which is the input area of the basal ganglia, a set of deep brain nuclei that help organise voluntary movement. At the striatum they release the chemical messenger dopamine.
Dopamine normally helps one route through the basal ganglia, the direct pathway, to release movement, and it restrains a second route, the indirect pathway, which suppresses movement. When the dopamine supply is lost, the balance of signals is upset and movement is impaired.
The result is slowness of movement (bradykinesia), stiffness (rigidity) and a resting tremor, a shake that is easiest to see when the limb is relaxed.
Symptoms usually appear only after about half of these neurons have been lost, so the process has often been under way for some time before the first symptom. The neurons that survive contain Lewy bodies, clumps of the protein alpha-synuclein, which are the typical microscopic finding.
Key facts
- Site of loss
- the substantia nigra pars compacta, a pigmented group of cells in the midbrain.
- Chemical lost
- dopamine, which these neurons normally deliver to the striatum.
- Threshold
- symptoms usually show up once about half of the dopamine-producing neurons have gone.
- Main features
- bradykinesia (slowness of movement), rigidity (stiffness) and resting tremor.
- Microscopic finding
- Lewy bodies (clumps of alpha-synuclein protein) are seen in the neurons that survive.
- Levodopa response
- a clear improvement on levodopa, which is converted to dopamine in the brain, supports idiopathic Parkinson's disease (Parkinson's disease of unknown cause) over its look-alikes.
Exam traps
- Autoimmune destruction of acetylcholine receptors is myasthenia gravis, where antibodies attack the receptors at the point where nerve meets muscle. It is a peripheral disorder of nerve-to-muscle signalling and does not cause resting tremor or rigidity, so it is not the change in Parkinson's disease.
- Dopaminergic neurones in the ventral tegmental area (an area next to the substantia nigra that also uses dopamine) are a near miss. Their neurones send dopamine to a different target, not to the part of the striatum that serves movement, so they do not account for the movement features.
- Huntington's disease also involves the basal ganglia, which makes it tempting. There the striatal neurons that release GABA (an inhibitory chemical messenger) are lost, giving chorea (excess jerky involuntary movement), whereas losing dopamine neurons of the substantia nigra leaves a poverty of movement (too little movement).
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