Dopamine acetylcholine imbalance in Parkinson's disease. Possible regenerative overgrowth of cholinergic axon terminals.

Parkinson's disease is characterised by an imbalance between acetylcholine and dopamine which probably results from the degeneration of a dopaminergic nigrostriatal pathway. A new hypothesis is proposed to explain the development of this imbalance. Applying the concept that degeneration of nerve-fibres in the central nervous system can lead to collateral sprouting of uninjured fibres, it is suggested that the death of dopaminergic nigrostriatal neurons results in sprouting of axons of cholinergic interneurons in the caudate nucleus. This overgrowth could result in the cholinergic innervation of neuronal membranes vacated by degenerated dopaminergic terminals. Thus, the apparent changes in the activity of dopaminergic and cholinergic systems can be accounted for by faulty regeneration in the central nervous system.