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Role of reactive nitrogen and reactive oxygen species against MPTP neurotoxicity in mice.
J Neural Transm (Vienna). 2008 Jun; 115(6):831-42.JN

Abstract

There is growing evidence indicating that reactive nitrogen species (RNS) and reactive oxygen species (ROS) are a major contributor to the pathogenesis and progression of Parkinson's disease. Here we investigated whether edaravone (free radical scavenger), minocycline (inducible nitric oxide synthase, iNOS inhibitor), 7-nitroindazole (neuronal NOS, nNOS inhibitor), fluvastatin (endothelial NOS, eNOS activator) and pitavastatin (eNOS activator) can protect against MPTP neurotoxicity in mice under the same condition. The present study showed that 7-nitroindazole could protect dose-dependently against the striatal dopamine depletions in mice 5 days after MPTP treatment. In contrast, edaravone, minocycline, fluvastatin and pitavastatin did not show the neuroprotective effect on MPTP-induced striatal dopamine depletion. Our immunohistochemical study showed that TH (tyrosine hydroxylase) and DAT (dopamine transporter) immunoreactivity was decreased significantly in the striatum and substantia nigra 5 days after MPTP treatment. The administration of 7-nitroindazole showed a protective effect against the severe reductions in levels of TH and DAT immunoreactivity in the striatum and substantia nigra 5 days after MPTP treatment. Furthermore, our Western blot analyses study showed the remarkable loss of TH protein levels in the striatum 5 days after MPTP treatment. In contrast, 7-nitroindazole prevented a significant loss in TH protein levels in the striatum 5 days after MPTP treatment. On the other hand, GFAP (glial fibrillary acidic protein) immunoreactivity increased significantly in the striatum and substantia nigra, 5 days after MPTP treatment. 7-Nitroindazole ameliorated severe increases in number of GFAP immunoreactive astrocytes in the striatum and substantia nigra 5 days after MPTP treatment. Furthermore, our Western blot analyses study showed the increase of GFAP protein levels in the striatum 5 days after MPTP treatment. 7-Nitroindazole prevented a significant increase in the GFAP protein levels in the striatum 5 days after MPTP treatment. The present results indicate that 7-nitroindazole can protect dose-dependently against the striatal dopamine depletions in mice 5 days after MPTP treatment. In contrast, edaravone, minocycline, fluvastatin and pitavastatin did not show the neuroprotective effect on MPTP-induced striatal dopamine depletions. These findings demonstrate that the overexpression of nNOS may play a major role in the neurotoxic processes of MPTP, as compared to the production of ROS, the overexpression of iNOS and the modulation of eNOS. Thus, our findings provide strong evidence for neuroprotective properties of nNOS inhibitor in this animal model of Parkinson's disease.

Authors+Show Affiliations

Department of Neurobiology and Therapeutics, Graduate School and Faculty of Pharmaceutical Sciences, The University of Tokushima, Tokushima, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18235988

Citation

Yokoyama, Hironori, et al. "Role of Reactive Nitrogen and Reactive Oxygen Species Against MPTP Neurotoxicity in Mice." Journal of Neural Transmission (Vienna, Austria : 1996), vol. 115, no. 6, 2008, pp. 831-42.
Yokoyama H, Takagi S, Watanabe Y, et al. Role of reactive nitrogen and reactive oxygen species against MPTP neurotoxicity in mice. J Neural Transm (Vienna). 2008;115(6):831-42.
Yokoyama, H., Takagi, S., Watanabe, Y., Kato, H., & Araki, T. (2008). Role of reactive nitrogen and reactive oxygen species against MPTP neurotoxicity in mice. Journal of Neural Transmission (Vienna, Austria : 1996), 115(6), 831-42. https://doi.org/10.1007/s00702-008-0019-6
Yokoyama H, et al. Role of Reactive Nitrogen and Reactive Oxygen Species Against MPTP Neurotoxicity in Mice. J Neural Transm (Vienna). 2008;115(6):831-42. PubMed PMID: 18235988.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of reactive nitrogen and reactive oxygen species against MPTP neurotoxicity in mice. AU - Yokoyama,Hironori, AU - Takagi,Sho, AU - Watanabe,Yu, AU - Kato,Hiroyuki, AU - Araki,Tsutomu, Y1 - 2008/01/31/ PY - 2007/09/03/received PY - 2008/01/07/accepted PY - 2008/2/1/pubmed PY - 2008/10/4/medline PY - 2008/2/1/entrez SP - 831 EP - 42 JF - Journal of neural transmission (Vienna, Austria : 1996) JO - J Neural Transm (Vienna) VL - 115 IS - 6 N2 - There is growing evidence indicating that reactive nitrogen species (RNS) and reactive oxygen species (ROS) are a major contributor to the pathogenesis and progression of Parkinson's disease. Here we investigated whether edaravone (free radical scavenger), minocycline (inducible nitric oxide synthase, iNOS inhibitor), 7-nitroindazole (neuronal NOS, nNOS inhibitor), fluvastatin (endothelial NOS, eNOS activator) and pitavastatin (eNOS activator) can protect against MPTP neurotoxicity in mice under the same condition. The present study showed that 7-nitroindazole could protect dose-dependently against the striatal dopamine depletions in mice 5 days after MPTP treatment. In contrast, edaravone, minocycline, fluvastatin and pitavastatin did not show the neuroprotective effect on MPTP-induced striatal dopamine depletion. Our immunohistochemical study showed that TH (tyrosine hydroxylase) and DAT (dopamine transporter) immunoreactivity was decreased significantly in the striatum and substantia nigra 5 days after MPTP treatment. The administration of 7-nitroindazole showed a protective effect against the severe reductions in levels of TH and DAT immunoreactivity in the striatum and substantia nigra 5 days after MPTP treatment. Furthermore, our Western blot analyses study showed the remarkable loss of TH protein levels in the striatum 5 days after MPTP treatment. In contrast, 7-nitroindazole prevented a significant loss in TH protein levels in the striatum 5 days after MPTP treatment. On the other hand, GFAP (glial fibrillary acidic protein) immunoreactivity increased significantly in the striatum and substantia nigra, 5 days after MPTP treatment. 7-Nitroindazole ameliorated severe increases in number of GFAP immunoreactive astrocytes in the striatum and substantia nigra 5 days after MPTP treatment. Furthermore, our Western blot analyses study showed the increase of GFAP protein levels in the striatum 5 days after MPTP treatment. 7-Nitroindazole prevented a significant increase in the GFAP protein levels in the striatum 5 days after MPTP treatment. The present results indicate that 7-nitroindazole can protect dose-dependently against the striatal dopamine depletions in mice 5 days after MPTP treatment. In contrast, edaravone, minocycline, fluvastatin and pitavastatin did not show the neuroprotective effect on MPTP-induced striatal dopamine depletions. These findings demonstrate that the overexpression of nNOS may play a major role in the neurotoxic processes of MPTP, as compared to the production of ROS, the overexpression of iNOS and the modulation of eNOS. Thus, our findings provide strong evidence for neuroprotective properties of nNOS inhibitor in this animal model of Parkinson's disease. SN - 0300-9564 UR - https://www.unboundmedicine.com/medline/citation/18235988/Role_of_reactive_nitrogen_and_reactive_oxygen_species_against_MPTP_neurotoxicity_in_mice_ L2 - https://doi.org/10.1007/s00702-008-0019-6 DB - PRIME DP - Unbound Medicine ER -