[EFFECT OF QUERCETIN ON NEURODEGENERATIVE AND COMPENSATORY PROCESSES IN NIGROSTRIATAL SYSTEM IN A MODEL OF PRECLINICAL PARKINSON''S DISEASE STAGE IN RATS]

Ross Fiziol Zh Im I M Sechenova. 2016 Jun;102(6):647-58.
[Article in Russian]

Abstract

Data on HSP70 involvement in Parkinson's disease (PD) pathogenesis, received in last 10 years, cannot answer the question whether the decrease in stress-inducible Hsp70 brain expression is one of the reasons for progressive neurodegeneration in PD. In the present study, the inhibitor of HSPs expression quercetin was used in a rat model of nigrostriatal system proteasome dysfunction. This model was created by the microinjections of the specific proteasome activity inhibitor lactacystin, that was injected locally to the substantia nigra pars compacta (SNpc). The model reproduces the under-threshold level of nigrostriatal degeneration and neurochemical features characteristic of the preclinical PD stage. It was shown for the first time that quercetin pretreatment inhibited the LC-induced expression of Hsp70 in the SNpc neurons and increased in 1.5 times the dopamine (DA)-ergic neurons death and in 2.7 times the striatal DA-ergic axons degeneration. These changes were accompanied by the depletion of compensatory mechanisms and HSP70 content in the SNpc neurons and the appearance of the motor dysfunctions, typical for the clinical PD stage. The results of this investigation indicate the important role of Hsp70 in mechanisms of the nigrostriatal system protection in proteasome dysfunction, characteristic for the pre-clinical PD stage. The data obtained can be considered as the scientific basis for the development of new technologies for early PD therapy by exogenous Hsp70.

MeSH terms

  • Acetylcysteine / adverse effects
  • Acetylcysteine / analogs & derivatives
  • Acetylcysteine / pharmacology
  • Animals
  • Corpus Striatum / metabolism*
  • Corpus Striatum / pathology
  • Corpus Striatum / physiopathology
  • Dopaminergic Neurons / metabolism*
  • Dopaminergic Neurons / pathology
  • HSP70 Heat-Shock Proteins / biosynthesis
  • Male
  • Neurodegenerative Diseases / drug therapy*
  • Neurodegenerative Diseases / metabolism
  • Neurodegenerative Diseases / pathology
  • Neurodegenerative Diseases / physiopathology
  • Parkinson Disease, Secondary / drug therapy*
  • Parkinson Disease, Secondary / metabolism
  • Parkinson Disease, Secondary / pathology
  • Parkinson Disease, Secondary / physiopathology
  • Proteasome Endopeptidase Complex / metabolism
  • Proteasome Inhibitors / adverse effects
  • Proteasome Inhibitors / pharmacology
  • Quercetin / pharmacology*
  • Rats
  • Rats, Wistar
  • Substantia Nigra / metabolism*
  • Substantia Nigra / pathology
  • Substantia Nigra / physiopathology

Substances

  • HSP70 Heat-Shock Proteins
  • Proteasome Inhibitors
  • lactacystin
  • Quercetin
  • Proteasome Endopeptidase Complex
  • Acetylcysteine