NEUROPROTECTIVE EFFECTS OF AAV2-hIL-10 IN MOUSE MODEL OF PARKINSON'S DISEASE

Parkinson's disease (PD) is a neurodegenerative disorder which is characterized by abnormal loss of nigrostriatal dopamine (DA) neurons, accompanied by DA deficiency in the striatum. The pathomechanism by which DA neurons degenerate is still unknown, however, there is increasing evidence that is possible immunological mechanisms involvement in the etiopathogenesis of PD. The aim of the present study was to examine the effect of an adeno-associated viral type-2 (AAV2) vector containing human interleukin-10 (hIL-10) gene on dopaminergic system restoration in the murine model of PD induced by by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Male C57BL/6 mice 12 months-old were used in this study. MPTP was injected in four intraperitoneal injections at 1-h intervals. AAV2-hIL-10 vector was bilaterally administered into striatum at 14, 21 or 28 days prior to MPTP intoxication. Animals were sacrificed at 7 days following MPTP injection. Striatal DA, DOPAC, HVA concentrations were quantified by HPLC method; tyrosine hydroxylase (TH) mRNA expression was measured by RT-PCR method. MPTP treatment dramatically decreased DA concentration, significantly decreased TH mRNA gene expression. AAV2-hIL-10 exerted a neuroprotective effect upon dopaminergic system (lower decrease in DA concentration). Additionally, viral vector administration prevented depletion of TH mRNA expression induced by MPTP. Our data suggest that AAV2-hIL-10 may play a neuroprotective role in MPTP mouse model of PD.