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Parkinson’s disease (PD) is a neurodegenerative disorder which is characterized by abnormal loss of nigrostriatal dopamine (DA) neurons, accompanied by DA defi ciency 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 sacrifi ced at 7 days following MPTP injection. Striatal DA, DOPAC, HVA concentrations were quantifi ed by HPLC method; tyrosine hydroxylase (TH) mRNA expression was measured by RT-PCR method. MPTP treatment dramatically decreased DA concentration, signifi cantly 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.
Interleukine 10 (IL-10) – an antiinfl ammatory cytokine produced by lymphocytes and mononuclear phagocytes including microglia. IL10 modulates the biological activities of immune cells resulting in a decreased production of pro-infl ammatory mediators including cytokines, chemokines and adhesion molecules. 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 to evaluation of immune response to the AAV2-hIL-10 (measured as IFN-γ, GFAP and TGFβ mRNA expression) in the murine model of Parkinson’s disease (PD) induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Male C57BL/6 mice 12 months-old were used in this study. MPTP (40 mg/kg) 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 sacrifi ced by spinal cords dislocation at 7 days following MPTP injection. TGFβ, IFN-γ and GFAP mRNA expression was examined by RT-PCR method. MPTP treatment signifi cantly increased IFN-γ mRNA expression. AAV2-hIL-10 administration strongly increased IFN-γ as well as TGFβ and GFAP (21 and 28 day) gene expression compared to control and MPTP group. Our results point to the necessity of the reinterpretation of the role of the infl ammatory reaction in nerodegenerative processes
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