Neuroprotective effect of arundic acid, an astrocyte-modulating agent, in mouse brain against MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) neurotoxicity
| Autor: | Tsutomu Araki, Naoto Kadoguchi, Hitoshi Maegawa, Toshiki Himeda, Yuko Kamiyama, Hiroyuki Kato |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Male
Time Factors Parkinson's disease Tyrosine 3-Monooxygenase Dopamine Neurotoxins Substantia nigra Motor Activity Pharmacology Nitric Oxide medicine.disease_cause Models Biological Neuroprotection Superoxide dismutase Mice Cellular and Molecular Neuroscience chemistry.chemical_compound medicine Animals Drug Interactions Brain Chemistry Dopamine Plasma Membrane Transport Proteins Behavior Animal biology Superoxide Dismutase MPTP Neurotoxicity Brain Homovanillic Acid medicine.disease Immunohistochemistry Mice Inbred C57BL Nitric oxide synthase Neuroprotective Agents nervous system chemistry Biochemistry 1-Methyl-4-phenyl-1 2 3 6-tetrahydropyridine biology.protein 3 4-Dihydroxyphenylacetic Acid Caprylates Nitric Oxide Synthase Oxidative stress |
| Zdroj: | Neuropharmacology. 50:329-344 |
| ISSN: | 0028-3908 |
| Popis: | 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes the damage of dopaminergic neurons as seen in Parkinson's disease. Oxidative stress has been as one of several pathogenic hypotheses for Parkinson's disease. Here we investigated whether arundic acid, an astrocyte-modulating agent, can protect against alterations of nitric oxide synthase (NOS) and superoxide dismutase (SOD) expression on MPTP neurotoxicity in mice, utilizing an immunohistochemistry. For this purpose, anti-tyrosine hydroxylase (TH) antibody, anti-dopamine transporter (DAT) antibody, anti-Cu/Zn-SOD antibody, anti-Mn-SOD antibody, anti-nNOS antibody, anti-eNOS antibody and anti-iNOS antibody were used. The present study showed that the arundic acid had a protective effect against MPTP-induced neuronal damage in the striatum and substantia nigra of mice. The protective effect may be, at least in part, caused by the reductions of the levels of reactive nitrogen (RNS) and oxygen species (ROS) against MPTP neurotoxicity. These results suggest that the pharmacological modulation of astrocyte may offer a novel therapeutic strategy for the treatment of Parkinson's disease. Furthermore, our results provide further evidence that a combination of nNOS inhibitors, iNOS inhibitors and free radical scavengers may be effective in the treatment of neurodegenerative diseases. Thus our present results provide valuable information for the pathogenesis of degeneration of the nigrostriatal dopaminergic neuronal pathway. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect