[Study of age changes in compensatory processes on the model of neurodegeneration of nigrostriatal system in rats.]

It is generally accepted that advanced age is the main risk factor for the development and progression of Parkinson's disease (PD). However, data that experimentally confirm the dependence on the age of the rate of neurodegeneration progression and the activity of compensatory processes in the nigrostriatal system in the development of PD are absent in the modern literature. The present study uses a model of neurodegeneration of the nigrostriatal system in rats of different age groups, created by the microinjections of the proteasome inhibitor lactacystin (LC) into the substantia nigra pars compacta (SNpc). The model reproduces the main pathomorphological signs of PD with great reliability. It is shown for the first time that LC administration to old rats, in comparison with young and middle-aged, causes more pronounced neurodegenerative changes in the nigrostriatal system, associated with impairments of fine motor function, a decrease in the growth of the stress-inducible heat shock protein Hsp70 in surviving neurons of SNpc and a decrease in the tyrosine hydroxylase and the vesicular monoamine transporter 2 contents. The data obtained allow us to summarize that the ageing-related weakening of Hsp70 expression combined with a decrease in the efficiency of compensatory processes are significant factors that determine the progression of pathology in the nigrostriatal system in the modeling of PD in old rats. The demonstrated age-related loss of compensatory mechanisms may be one of the reasons for the rapid PD progression in the elderly.