The influence of AAV2-mediated gene transfer of human IL-10 on neurodegeneration and immune response in a murine model of Parkinson's disease

• Published in: Pharmacological reports Vol. 66; no. 4; p. 660
• Main Authors: Joniec-Maciejak, Ilona, Ciesielska, Agnieszka, Wawer, Adriana, Sznejder-Pachołek, Anna, Schwenkgrub, Joanna, Cudna, Agnieszka, Hadaczek, Piotr, Bankiewicz, Kristof S, Członkowska, Anna, Członkowski, Andrzej
• Format: Journal Article
• Language: English
• Published: Switzerland 01-08-2014
• Subjects: Animals; Corpus Striatum - immunology; Corpus Striatum - metabolism; Corpus Striatum - pathology; Dependovirus - genetics; Disease Models, Animal; Dopamine - metabolism; Dopaminergic Neurons - enzymology; Dopaminergic Neurons - immunology; Dopaminergic Neurons - pathology; Enzyme-Linked Immunosorbent Assay; Gene Expression Regulation; Gene Transfer Techniques; Genetic Vectors; Humans; Immunohistochemistry; Interleukin-10 - genetics; Interleukin-10 - immunology; Male; Mice, Inbred C57BL; Parkinsonian Disorders - immunology; Parkinsonian Disorders - pathology; Parkinsonian Disorders - therapy; Reverse Transcriptase Polymerase Chain Reaction; Tyrosine 3-Monooxygenase - metabolism; Neuroprotection; Adeno-associated virus; Inflammation; Parkinson's disease; MPTP
• ISSN: 1734-1140
• DOI: 10.1016/j.pharep.2014.03.008

The aim of this study was to examine the effect of AAV2-hIL-10 (vector containing cDNA for human interleukin 10) on dopaminergic system activity (measured as DA levels and TH mRNA expression in mouse striata), and other monoamine and amino acid neurotransmitters concentration as well as development of inflammatory processes (measured as TGF-β, IFN-γ and GFAP mRNA expression) in a murine MPTP neurotoxicant model of Parkinson's disease.
Male C57BL/6 mice 12 months-old were used in this study. 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. The expression of hIL-10 (human interleukin 10) was examined by ELISA. Striatal monoamine and amino acid neurotransmitters were measured by HPLC method. TH, TGF-β, IFN-γ and GFAP mRNA expression was examined by RT-PCR method.
MPTP treatment dramatically reduced DA levels and decreased TH mRNA expression in mouse striata, effects that were significantly impeded by AAV2-hIL-10 administration prior to MPTP intoxication. AAV2-hIL-10 infusion increased IFN-γ, TGF-β and GFAP mRNA expression.
Our data suggest that the transfer of AAV2-hIL-10 into the striatum may play a neuroprotective role in the mouse MPTP model of PD and these effects are mediated by the anti-inflammatory action of IL-10.