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MPTP induced degeneration of nigrostriatal DA neurons and glial activation as visualized by tyrosine hydroxylase, macrophage Ag complex-1, and\/or glial fibrillary acidic protein immunoreactivity. Real-time PCR, Western blotting, and immunohistochemistry showed upregulation of proinflammatory cytokines, activation of microglial NADPH oxidase and astroglial myeloperoxidase, and subsequent reactive oxygen species production and oxidative DNA damage in the MPTP-treated substantia nigra. Treatment with paroxetine prevented degeneration of nigrostriatal DA neurons, increased striatal dopamine levels, and improved motor function. This neuroprotection afforded by paroxetine was associated with the suppression of astroglial myeloperoxidase expression and\/or NADPH oxidase-derived reactive oxygen species production and reduced expression of proinflammatory cytokines, including IL-1\u03b2, TNF-\u03b1, and inducible NO synthase, by activated microglia. The present findings show that paroxetine may possess anti-inflammatory properties and inhibit glial activation-mediated oxidative stress, suggesting that paroxetine and its analogues may have therapeutic value in the treatment of aspects of Parkinson\u2019s disease related to neuroinflammation.<\/jats:p>","DOI":"10.4049\/jimmunol.1000208","type":"journal-article","created":{"date-parts":[[2010,6,21]],"date-time":"2010-06-21T22:42:58Z","timestamp":1277160178000},"page":"1230-1237","source":"Crossref","is-referenced-by-count":124,"title":["Paroxetine Prevents Loss of Nigrostriatal Dopaminergic Neurons by Inhibiting Brain Inflammation and Oxidative Stress in an Experimental Model of Parkinson\u2019s Disease"],"prefix":"10.1093","volume":"185","author":[{"given":"Young C","family":"Chung","sequence":"first","affiliation":[{"name":"Neuroscience Graduate Program, School of Medicine, Ajou University , Seoul ,","place":["South Korea"]},{"name":"Division of Cell Transformation and Restoration, School of Medicine, Ajou University , Suwon ,","place":["South Korea"]},{"name":"Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University , Seoul ,","place":["South Korea"]},{"name":"Neurodegeneration Control Research Center, School of Medicine, Kyung Hee University , Seoul ,","place":["South Korea"]},{"name":"Aged-Related and Brain Disease Research Center, School of Medicine, Kyung Hee University , Seoul ,","place":["South Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang R","family":"Kim","sequence":"additional","affiliation":[{"name":"Neuroscience Graduate Program, School of Medicine, Ajou University , Seoul ,","place":["South Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byung K","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University , Seoul ,","place":["South Korea"]},{"name":"Neurodegeneration Control Research Center, School of Medicine, Kyung Hee University , Seoul ,","place":["South Korea"]},{"name":"Aged-Related and Brain Disease Research Center, School of Medicine, Kyung Hee University , Seoul ,","place":["South Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2010,7,15]]},"reference":[{"key":"2025032411392437300_r1","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/S0896-6273(03)00568-3","article-title":"Parkinson\u2019s disease: mechanisms and models","volume":"39","author":"Dauer","year":"2003","journal-title":"Neuron"},{"key":"2025032411392437300_r2","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1146\/annurev.neuro.22.1.123","article-title":"Etiology and pathogenesis of Parkinson\u2019s disease","volume":"22","author":"Olanow","year":"1999","journal-title":"Annu. 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