Detection of the latent functional insufficiency of dopaminergic neurons in the nigrostriatal system in a chronic model of Parkinson’s disease

Abstract

The most important component of the pathogenesis of Parkinson’s disease is the degradation of the nigrostriatal dopaminergic system, which is a key link in the regulation of motor function. Impaired motor function, and, consequently, the possibility of diagnosing the disease, occur only 20–30 years after the onset of the pathological process with the death of 50–60% of dopaminergic neurons and a decrease in the level of synthesis of dopamine in the striatum by 70–80%. The lack of effective therapy is associated with the late diagnosis of the disease, when there are practically no targets for pharmacotherapy. Therefore, one of the most important priorities of modern neurology is the development of a method for the early diagnosis of Parkinson’s disease at the preclinical (asymptomatic) stage. In this work, a new approach was developed to assess the functional deficiency of the dopaminergic nigrostriatal system using an inhibitor of dopamine-α-methyl-p-tyrosine synthesis in a chronic model of the preclinical stage of Parkinson’s disease in mice. Administration of α-methyl-p-tyrosine to animals in a model of the preclinical stage of Parkinson’s disease led to the appearance of motor behavior disorders but not in the control group. These data point to the possibility of using this approach as a provocative test for the diagnosis of this disease at the preclinical stage, which will allow us to begin treatment aimed at slowing the death of dopaminergic neurons.