Parkinson's disease focusing on neuronal systems

Abstract

Parkinson's Disease (PD) is a progressive degenerative neurological disorder characterized by resting tremor, bradykinesia, cogwheel rigidity, and postural instability. These symptoms result primarily from the loss of dopaminergic neurons in the substantia nigra. Positron emission tomography (PET) has enabled the acquisition of in vivo images of dopamine metabolism in patients with PD. Human endogenous dopamine level peaks at around 20 years old, and is decreased in 10 to 13% per decade of life. Some studies indicated that 80% loss of dopaminergic neurons in the substantia nigra was needed to develop symptoms of Parkinson's disease. Because many compensation systems are working against the decrease of dopamine. One of the most famous systems is acetylcholine. The striatal medium spiny neuron is regulated by dopaminergic input from substantia nigra pars compacta and cholinergic ineterneurons. Cholinergic interneurons occupy 1 to 2% of the neurons in the striatum. Nigral dopaminergic neurons suppress cholinergic interneurons in the striatum. In Parkinson's disease, the cholinergic system is relatively dominant because of degeneration of dopaminergic neurons. Anticholinergic reverses the balance of acetylcholine dominance. Using PET, we have shown that sigma₁ and adenosine A_2A receptors are involved in the compensation of dopamine deficiency.