The influence of AAV-mediated gene transfer of human interleukin 10 on the neurodegenerative process in the murine model of parkinson's disease

• Autorzy: Wawer A. , Joniec-Maciejak I. , Schwenkgrub J. , Sznejder A. , Ciesielska A. , Bankiewicz K. , Czlonkowska A. , Czlonkowski A.
• Języki publikacji: EN

Abstrakty

EN

Parkinson’s disease (PD) is one of the most common neurodegenerative disorders. It is characterized by a progressive loss of dopaminergic neurons, which occurs mainly in the substantia nigra (SN), resulting in the loss of nerve terminals, accompanied by a decreased concentration of dopamine (DA) and its metabolites in the striatum. Concurrently with neurodegeneration, a chronic inflammation occurs in the affected regions of the brain. Mechanisms and etiology of the neurodegeneration are still unknown. One potential strategy for therapy of PD is to reduce the neurodegeneration by inhibiting the inflammatory reaction. Nowadays, there are high hopes for the gene therapy based treatment. This involves using a noninfectious virus administered directly into the brain. In this study a transfer of AAV vector containing the complementary DNA for human interleukin 10 (IL-10) into the nigrostriatal pathway was used. IL-10 is one of the major antiinflammatory cytokines. The aim of the present study was to examine the expression of human IL-10, administered into striatum by viral vector AAV2-hIL-10 and investigate the influence of this cytokine on neurodegenerative process in the murine model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). One year old male C57Bl mice were used in this study. The expression of human IL-10 was measured by enzyme-linked immunosorbent assay (ELISA). To evaluate the influence of the human IL-10 on neurodegeneration concentrations of striatal DA, 3,4-dihydroxyphenyl acetic acid and homovanillic acid were measured by high performance liquid chromatography (HPLC). The findings demonstrate human IL-10 secretion in the mouse brain after striatal infusion of AAV2-hIL-10. This study suggests that human IL-10 delivered by an AAV2 vector preserves nigrostriatal function after MPTP intoxication (lower decrease in DA concentration). IL-10 can play a vital role in inhibition of inflammatory reaction or surviving cells stimulation.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2011
• Tom: 71
• Numer: S
• Opis fizyczny: p.70

Twórcy

autor

Wawer A.

• Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Warsaw, Poland

autor

Joniec-Maciejak I.

• Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Warsaw, Poland

autor

Schwenkgrub J.

• Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Warsaw, Poland

autor

Sznejder A.

• Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Warsaw, Poland

autor

Ciesielska A.

• Department of Neurosurgery, University of California San Francisco, San Francisco, USA

autor

Bankiewicz K.

• Department of Neurosurgery, University of California San Francisco, San Francisco, USA

autor

Czlonkowska A.

• Second Department of Neurology, Institute of Psychiatry and Neurology, Warsaw, Poland

autor

Czlonkowski A.

• Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Warsaw, Poland

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