Paroxetine prevents loss of nigrostriatal dopaminergic neurons by inhibiting brain inflammation and oxidative stress in an experimental model of Parkinson's disease

The present study examined whether the antidepressant paroxetine promotes the survival of nigrostriatal dopaminergic (DA) neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease. MPTP induced degeneration of nigrostriatal DA neurons and glial activa...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of immunology (1950) 2010-07, Vol.185 (2), p.1230-1237
Main Authors: Chung, Young C, Kim, Sang R, Jin, Byung K
Format: Article
Language:English
Subjects:
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Animals
Antidepressive Agents, Second-Generation - pharmacology
Blotting, Western
Brain - drug effects
Brain - metabolism
Brain - pathology
Dopamine - metabolism
Enzyme Activation - drug effects
Immunohistochemistry
Inflammation - chemically induced
Inflammation - genetics
Inflammation - metabolism
Interleukin-1beta - genetics
Interleukin-1beta - metabolism
Male
Mice
Mice, Inbred C57BL
Motor Activity - drug effects
NADPH Oxidases - antagonists & inhibitors
NADPH Oxidases - metabolism
Neurons - drug effects
Neurons - metabolism
Nitric Oxide Synthase Type II - genetics
Nitric Oxide Synthase Type II - metabolism
Oxidative Stress - drug effects
Parkinson Disease, Secondary - chemically induced
Parkinson Disease, Secondary - physiopathology
Parkinson Disease, Secondary - prevention & control
Paroxetine - pharmacology
Peroxidase - metabolism
Reverse Transcriptase Polymerase Chain Reaction
Substantia Nigra - cytology
Substantia Nigra - drug effects
Substantia Nigra - metabolism
Tumor Necrosis Factor-alpha - genetics
Tumor Necrosis Factor-alpha - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The present study examined whether the antidepressant paroxetine promotes the survival of nigrostriatal dopaminergic (DA) neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease. 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-1beta, TNF-alpha, 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's disease related to neuroinflammation.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.1000208