Fluoxetine prevents MPTP-induced loss of dopaminergic neurons by inhibiting microglial activation
| Autor: | Ju Young Park, Eun S. Park, Hyuk Wan Ko, Eun Sook Chung, Eugene Bok, Sung Hwa Yoon, Young Cheul Chung, So Y. Won, Byung Kwan Jin, Yoon Seong Kim, Keun W. Park, Sang Ryong Kim, Minyoung Jin |
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| Rok vydání: | 2011 |
| Předmět: |
Male
1-Methyl-4-phenylpyridinium Dopamine Nitric Oxide Synthase Type II Cell Count Substantia nigra Pharmacology medicine.disease_cause Neuroprotection Mice Cellular and Molecular Neuroscience chemistry.chemical_compound Fluoxetine medicine Animals Reactive nitrogen species Neuroinflammation Neurons MPTP Dopaminergic Neurotoxicity MPTP Poisoning NADPH Oxidases Recovery of Function medicine.disease Coculture Techniques Corpus Striatum Mice Inbred C57BL Substantia Nigra Oxidative Stress Neuroprotective Agents nervous system chemistry 1-Methyl-4-phenyl-1 2 3 6-tetrahydropyridine Rotarod Performance Test Nerve Degeneration Cytokines Microglia Neuroscience Oxidative stress |
| Zdroj: | Neuropharmacology. 60:963-974 |
| ISSN: | 0028-3908 |
| Popis: | Parkinson's disease (PD) is characterized by degeneration of nigrostriatal dopaminergic (DA) neurons. Mice treated with MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) exhibit microglial activation-induced oxidative stress and inflammation, and nigrostriatal DA neuronal damage, and thus serve as an experimental model of PD. Here, we report that fluoxetine, one of the most commonly prescribed antidepressants, prevents MPTP-induced degeneration of nigrostriatal DA neurons and increases striatal dopamine levels with the partial motor recovery. This was accompanied by inhibiting transient expression of proinflammatory cytokines and inducible nitric oxide synthase; and attenuating microglial NADPH oxidase activation, reactive oxygen species/reactive nitrogen species production, and consequent oxidative damage. Interestingly, fluoxetine was found to protect DA neuronal damage from 1-methyl-4-phenyl-pyridinium (MPP(+)) neurotoxicity in co-cultures of mesencephalic neurons and microglia but not in neuron-enriched mesencephalic cultures devoid of microglia. The present in vivo and in vitro findings show that fluoxetine may possess anti-inflammatory properties and inhibit glial activation-mediated oxidative stress. Therefore, we carefully propose that neuroprotection of fluoxetine might be associated with its anti-inflammatory properties and could be employed as novel therapeutic agents for PD and other disorders associated with neuroinflammation and microglia-derived oxidative damage. |
| Databáze: | OpenAIRE |
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