CNS compensation to dopamine neuron loss in Parkinson's disease

Postmortem studies in brains from parkinsonian patients consistently reveal a minimum loss of 75% of the nigrostriatal dopamine neurons. This indicates that over a prolonged period, before Parkinson's disease is clinically evident, there is a physiological compensation for the slow loss of dopamine neurons (i.e. compensated stage of Parkinson's disease). Only when the dopamine neuron loss is sufficiently severe (greater than 75% of nigrostriatal dopamine neurons) does the disease become clinically evident (decompensated state). Postmortem examination of Parkinson's disease brains and study of animal models indicate that the following mechanisms may contribute to this CNS compensation: 1) A decrease in striatal cholinergic activity, in an attempt to maintain a critical DA:ACh balance; and 2) A decrease in activity of GABA neurons in the striatum and substantia nigra, resulting in an increased firing rate of nigral dopamine cells. These mechanisms allow the brain to readjust to the initial dopamine cell loss in Parkinson's disease.