 |
||||
|
||||
|
||||
|
||||
|
||||
Previous Article | Next Article
The Journal of Neuroscience, February 1, 2002, 22(3):782-790
Distinct Role for Microglia in Rotenone-Induced Degeneration of Dopaminergic Neurons
Hui-Ming Gao1, 2, Jau-Shyong Hong1, Wanqin Zhang2, and Bin Liu1 1 Neuropharmacology Section, Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, and 2 Department of Physiology, Dalian Medical University, Dalian, 116027, China
Increasing evidence has suggested an important role for environmental factors such as exposure to pesticides in the pathogenesis of Parkinson's disease. In experimental animals the exposure to a common herbicide, rotenone, induces features of parkinsonism; mechanistically, rotenone-induced destruction of dopaminergic neurons has been attributed to its inhibition of the activity of neuronal mitochondrial complex I. However, the role of microglia, the resident brain immune cells in rotenone-induced neurodegeneration, has not been reported. Using primary neuron-enriched and neuron/glia cultures from the rat mesencephalon, we discovered an extraordinary feature for rotenone-induced degeneration of cultured dopaminergic neurons. Although little neurotoxicity was detected in neuron-enriched cultures after treatment for 8 d with up to 20 nM rotenone, significant and selective dopaminergic neurodegeneration was observed in neuron/glia cultures 2 d after treatment with 20 nM rotenone or 8 d after treatment with 1 nM rotenone. The greatly enhanced neurodegenerative ability of rotenone was attributed to the presence of glia, especially microglia, because the addition of microglia to neuron-enriched cultures markedly increased their susceptibility to rotenone. Mechanistically, rotenone stimulated the release of superoxide from microglia that was attenuated by inhibitors of NADPH oxidase. Furthermore, inhibition of NADPH oxidase or scavenging of superoxide significantly reduced the rotenone-induced neurotoxicity. This is the first report demonstrating that microglia play a pivotal role in rotenone-induced degeneration of dopaminergic neurons. The results of this study should advance our understanding of the mechanism of action for pesticides in the pathogenesis of Parkinson's disease.
Key words: pesticides; microglia; superoxide; dopamine; Parkinson's disease; neurotoxicity
Copyright © 2002 Society for Neuroscience 0270-6474/02/223782-09$05.00/0
This article has been cited by other articles:
X. Hu, D. Zhang, H. Pang, W. M. Caudle, Y. Li, H. Gao, Y. Liu, L. Qian, B. Wilson, D. A. Di Monte, et al.
Macrophage Antigen Complex-1 Mediates Reactive Microgliosis and Progressive Dopaminergic Neurodegeneration in the MPTP Model of Parkinson's Disease
J. Immunol., November 15, 2008; 181(10): 7194 - 7204.
[Abstract] [Full Text] [PDF]
J. Z. Guan, T. Maeda, M. Sugano, J.-i. Oyama, Y. Higuchi, T. Suzuki, and N. Makino
A Percentage Analysis of the Telomere Length in Parkinson's Disease Patients
J. Gerontol. A Biol. Sci. Med. Sci., May 1, 2008; 63(5): 467 - 473.
[Abstract] [Full Text] [PDF]
M.-J. Wang, S.-Z. Lin, J.-S. Kuo, H.-Y. Huang, S.-F. Tzeng, C.-H. Liao, D.-C. Chen, and W.-F. Chen
Urocortin Modulates Inflammatory Response and Neurotoxicity Induced by Microglial Activation
J. Immunol., November 1, 2007; 179(9): 6204 - 6214.
[Abstract] [Full Text] [PDF]
H. Klintworth, K. Newhouse, T. Li, W.-S. Choi, R. Faigle, and Z. Xia
Activation of c-Jun N-Terminal Protein Kinase Is a Common Mechanism Underlying Paraquat- and Rotenone-Induced Dopaminergic Cell Apoptosis
Toxicol. Sci., May 1, 2007; 97(1): 149 - 162.
[Abstract] [Full Text] [PDF]
M. P. Mount, A. Lira, D. Grimes, P. D. Smith, S. Faucher, R. Slack, H. Anisman, S. Hayley, and D. S. Park
Involvement of Interferon-{gamma} in Microglial-Mediated Loss of Dopaminergic Neurons
J. Neurosci., March 21, 2007; 27(12): 3328 - 3337.
[Abstract] [Full Text] [PDF]
W. Zhang, E.-J. Shin, T. Wang, P. H. Lee, H. Pang, M.-B. Wie, W.-K. Kim, S.-J. Kim, W.-H. Huang, Y. Wang, et al.
3-Hydroxymorphinan, a metabolite of dextromethorphan, protects nigrostriatal pathway against MPTP-elicited damage both in vivo and in vitro
FASEB J, December 1, 2006; 20(14): 2496 - 2511.
[Abstract] [Full Text] [PDF]
M. K. McCoy, T. N. Martinez, K. A. Ruhn, D. E. Szymkowski, C. G. Smith, B. R. Botterman, K. E. Tansey, and M. G. Tansey
Blocking soluble tumor necrosis factor signaling with dominant-negative tumor necrosis factor inhibitor attenuates loss of dopaminergic neurons in models of Parkinson's disease.
J. Neurosci., September 13, 2006; 26(37): 9365 - 9375.
[Abstract] [Full Text] [PDF]
C. F. Orr, D. B. Rowe, Y. Mizuno, H. Mori, and G. M. Halliday
A possible role for humoral immunity in the pathogenesis of Parkinson's disease
Brain, November 1, 2005; 128(11): 2665 - 2674.
[Abstract] [Full Text] [PDF]
Y. Zhou, Y. Wang, M. Kovacs, J. Jin, and J. Zhang
Microglial Activation Induced by Neurodegeneration: A Proteomic Analysis
Mol. Cell. Proteomics, October 1, 2005; 4(10): 1471 - 1479.
[Abstract] [Full Text] [PDF]
F. Zoccarato, P. Toscano, and A. Alexandre
Dopamine-derived Dopaminochrome Promotes H2O2 Release at Mitochondrial Complex I: STIMULATION BY ROTENONE, CONTROL BY Ca2+, AND RELEVANCE TO PARKINSON DISEASE
J. Biol. Chem., April 22, 2005; 280(16): 15587 - 15594.
[Abstract] [Full Text] [PDF]
S.-H. Choi, D. Y. Lee, S. U. Kim, and B. K. Jin
Thrombin-Induced Oxidative Stress Contributes to the Death of Hippocampal Neurons In Vivo: Role of Microglial NADPH Oxidase
J. Neurosci., April 20, 2005; 25(16): 4082 - 4090.
[Abstract] [Full Text] [PDF]
W. Zhang, T. Wang, Z. Pei, D. S. Miller, X. Wu, M. L. Block, B. Wilson, W. Zhang, Y. Zhou, J.-S. Hong, et al.
Aggregated {alpha}-synuclein activates microglia: a process leading to disease progression in Parkinson's disease
FASEB J, April 1, 2005; 19(6): 533 - 542.
[Abstract] [Full Text] [PDF]
B. G. Ramirez, C. Blazquez, T. G. del Pulgar, M. Guzman, and M. L. de Ceballos
Prevention of Alzheimer's Disease Pathology by Cannabinoids: Neuroprotection Mediated by Blockade of Microglial Activation
J. Neurosci., February 23, 2005; 25(8): 1904 - 1913.
[Abstract] [Full Text] [PDF]
A. Y. Abramov, L. Canevari, and M. R. Duchen
{beta}-Amyloid Peptides Induce Mitochondrial Dysfunction and Oxidative Stress in Astrocytes and Death of Neurons through Activation of NADPH Oxidase
J. Neurosci., January 14, 2004; 24(2): 565 - 575.
[Abstract] [Full Text] [PDF]
H.-M. Gao, B. Liu, and J.-S. Hong
Critical Role for Microglial NADPH Oxidase in Rotenone-Induced Degeneration of Dopaminergic Neurons
J. Neurosci., July 16, 2003; 23(15): 6181 - 6187.
[Abstract] [Full Text] [PDF]
Y. Liu, L. Qin, G. Li, W. Zhang, L. An, B. Liu, and J.-S. Hong
Dextromethorphan Protects Dopaminergic Neurons against Inflammation-Mediated Degeneration through Inhibition of Microglial Activation
J. Pharmacol. Exp. Ther., April 1, 2003; 305(1): 212 - 218.
[Abstract] [Full Text]
H.-M. Gao, J.-S. Hong, W. Zhang, and B. Liu
Synergistic Dopaminergic Neurotoxicity of the Pesticide Rotenone and Inflammogen Lipopolysaccharide: Relevance to the Etiology of Parkinson's Disease
J. Neurosci., February 15, 2003; 23(4): 1228 - 1236.
[Abstract] [Full Text] [PDF]
B. Liu and J.-S. Hong
Role of Microglia in Inflammation-Mediated Neurodegenerative Diseases: Mechanisms and Strategies for Therapeutic Intervention
J. Pharmacol. Exp. Ther., January 1, 2003; 304(1): 1 - 7.
[Abstract] [Full Text] [PDF]
Y. Liu, L. Qin, B. C. Wilson, L. An, J.-S. Hong, and B. Liu
Inhibition by Naloxone Stereoisomers of beta -Amyloid Peptide (1-42)-induced Superoxide Production in Microglia and Degeneration of Cortical and Mesencephalic Neurons
J. Pharmacol. Exp. Ther., September 1, 2002; 302(3): 1212 - 1219.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|