Lactacystin-induced pathologically regressive changes of rat models of Parkinson's disease

Objective To observe the pathologically regressive changes of rat models of Parkinson's disease (PD) induced by Lactacystin (Lac), and to investigate the pathogenesis of PD.Methods Totally 32 SD rats were randomly divided into 2 groups: test group and control group. Lac, a selective proteasome inhibitor, was unilaterally injected stereotaxically into the left substantia nigral pars compacta (SNc) of rats. Equal volume of saline was injected in control group. On day 1, 3, 5, 7, 9, 11, 14 and 21 post-in jection, we observed the behavioral changes of the rats and pathological changes in substantial nigra and striatum, and detected the expressions of tyrosine hydroxylase (TH) and α-synuclein by immunohistochemistry (IHC) and HE staining and the expressions of their mRNA by RT-PCR. Results Behavioral changes were found in the rats of test group. By HE staining, after Lac-treatment, microglia was increased on the 1st day (3501.92±57.32), 4895.50±52.67 on day 7, 5340.18±52.87 on day 21 (P 0.05 vs control group 0.2412±0.0067); it was 0.0781±0.0013 on day 21, significantly different from control group 0.2412±0.0067 (P<0.05). Meanwhile, in the test group, the detection of mRNA expression displayed that TH neurons were reduced, while α-synuclein mRNA was accumulating in survival TH neurons. Conclusion Pathological changes in PD models induced by lactacystin are retrograde along with time going on, and consistent with the characters of delitescence and slow progressions in PD. Key words: Lactacystin;  Parkinson's disease;  Tyrosine hydroxylase;  α-synuclein