BACKGROUND: Parkinson's disease (PD) is the second most common progressive neurodegenerative disorder. The degeneration of the nigro-striatal pathway has been linked with the inflammatory process accompanied by the robust up-regulation of the nitric oxide synthase (NOS) and production of the neurotoxic level of nitric oxide (NO). One of the therapeutic strategies of PD is based on the reduction of the detrimental neuroinflammatory markers in the lesioned nigro-striatal pathway. In this study we have investigated the neuroprotective effect of the cerebral infusion of recombinant adeno-associated viral vector, expressing the gene for human interleukin-10 (AAV2-hIL-10) in a mouse model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). It is known that IL-10 is a potent anti-inflammatory cytokine that limits the inducible nitric oxide synthase (iNOS) gene expression. METHODS: The striatal iNOS, neuronal nitric oxide synthase (nNOS) and tyrosine hydroxylase (TH) protein expression was evaluated by immunoblot analysis. RESULTS: The intracerebral injection of the AAV2-hIL-10, before the lesion, induced the upregulation of the striatal TH protein, depleted by MPTP intoxication. This AAV2-hIL-10-induced increase of TH level was associated with the suppression of iNOS protein expression in the lesioned striatum. CONCLUSION: The results revealed protective properties of AAV2-hIL-10.
BACKGROUND:Parkinson's disease (PD) is the second most common progressive neurodegenerative disorder. The degeneration of the nigro-striatal pathway has been linked with the inflammatory process accompanied by the robust up-regulation of the nitric oxide synthase (NOS) and production of the neurotoxic level of nitric oxide (NO). One of the therapeutic strategies of PD is based on the reduction of the detrimental neuroinflammatory markers in the lesioned nigro-striatal pathway. In this study we have investigated the neuroprotective effect of the cerebral infusion of recombinant adeno-associated viral vector, expressing the gene for humaninterleukin-10 (AAV2-hIL-10) in a mouse model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). It is known that IL-10 is a potent anti-inflammatory cytokine that limits the inducible nitric oxide synthase (iNOS) gene expression. METHODS: The striatal iNOS, neuronal nitric oxide synthase (nNOS) and tyrosine hydroxylase (TH) protein expression was evaluated by immunoblot analysis. RESULTS: The intracerebral injection of the AAV2-hIL-10, before the lesion, induced the upregulation of the striatal TH protein, depleted by MPTP intoxication. This AAV2-hIL-10-induced increase of TH level was associated with the suppression of iNOS protein expression in the lesioned striatum. CONCLUSION: The results revealed protective properties of AAV2-hIL-10.
Authors: Tcs Costa; E Fernandez-Villalba; V Izura; A M Lucas-Ochoa; N J Menezes-Filho; R C Santana; M D de Oliveira; F M Araújo; C Estrada; Vda Silva; S L Costa; M T Herrero Journal: J Neuroimmune Pharmacol Date: 2020-06-21 Impact factor: 4.147