Study the dynamics of behavioral and biochemical parameters in the PARK2-knock-out mice model of Parkinson's disease

Abstract

BackgroundParkinsons disease (PD) is a progressive chronic neurodegenerative disease. The PARK2 gene encoding the Parkin protein accounts for approximately half of early-onset autosomal recessive PD cases in humans. ObjectiveThe aim of this work was to study the effect of the PARK2 gene knockout in mice on the dynamics of behavioral and biochemical parameters of PD. MethodsThe study was performed on C57BL/6-line mice aged from 4 months to 1.5 years: wild type (park2 +/+), heterozygotes (park2 +/-) and homozygotes (park2 -/-) knocked out by the PARK2 using CRISPR-Cas9. The open field test, the Porsolt forced swimming test, the grid-walk test, the beam-walking test, the elevated plus maze test, the accelerating rotarod test were used to assess the behavioral phenotype. Measurement of the concentration of bioamines and their metabolites by HPLC and evaluation of the amount of tyrosine hydroxylase, BDNF and GDNF by Western Blot were used to study the biochemical signs of PD. ResultsPark2 -/- mice begin to show signs of decreased motor activity no earlier than at 4 months of life. At 12 months of life, it was shown only a decrease in the level of the mature isoform of GDNF and an increase in the number of immature isoforms in the frontal cortex and striatum were revealed. ConclusionThe data obtained indicates a different age dynamic of the condition of mice associated with the PARK2 knockout. However, no pronounced specific manifestations of PD in human were found in park2 -/- mice.