Study of Age-Related Changes in Compensatory Processes in the Model of Neurodegeneration of the Nigrostriatal System in Rats

Abstract

It is generally accepted that old age is the main risk factor for the development and progression of Parkinson’s disease (PD). However, there is currently no data available that experimentally confirm the age dependence of the neurodegeneration progression rate and the activity of compensatory processes in the nigrostriatal system in the development of PD. The present study applies a model of nigrostriatal system neurodegeneration in rats of different ages, which was developed using the microinjections with proteasome inhibitor lactacystin (LC) into the substantia nigra pars compacta (SNpc). The model reproduces the main pathomorphological signs of PD with great reliability. It has been demonstrated that the administration of LC to old rats, compared to young and middle-aged ones, causes more pronounced neurodegenerative changes in the nigrostriatal system which are associated with impairments in 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 contents of tyrosine hydroxylase and the vesicular monoamine transporter 2. The data obtained suggest that the aging-related decrease in Hsp70 expression together with a decrease in the efficiency of compensatory processes is a significant factor which determines the progression of pathology in the nigrostriatal system in PD model in old rats. The age-related loss of compensatory mechanisms observed may be one of the causes of the rapid PD progression in the elderly.