Effects of Quercetin on Neurodegenerative and Compensatory Processes in the Nigrostriatal System in a Model of the Preclinical Stage of Parkinson’s Disease in Rats

Data obtained over the last ten years on the involvement of molecular chaperones of the heat shock protein 70 (HSP70) family in the pathogenesis of Parkinson's disease (PD) do not provide an answer to the question of whether a decrease in the expression of stress-inducible Hsp70 in the brain is one of the causes of progression of neurodegeneration in PD. The present study used the HSP expression inhibitor quercetin in a model of proteasomal dysfunction in the nigrostriatal system in rats created by microinjection of the proteasome inhibitor lactacystin into the compact zone of the substantia nigra (SNc). This model reproduces subthreshold levels of nigrostriatal system degradation and neurochemical changes present in the preclinical stage of PD. We provide the first demonstration that preventive administration of quercetin prevents LC-induced Hsp70 expression in SNc neurons and leads to a 1.5-fold increase in the degeneration of dopaminergic neurons in the SNc and a 2.7-fold increase in the number of dopaminergic neuron axons in the striatum, with depletion of compensation processes and HSP70 reserves in SNc neurons. Signs of motor dysfunction typical of the clinical stage of PD were seen. The study results confirm the important role of Hsp70 in the mechanisms of protection of the nigrostriatal system in proteasomal dysfunction typical of the preclinical stage of PD. These data may provide scientific grounds for developing new techniques for the early treatment of PD based on Hsp70 preparations.

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