![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Vol. 305, Issue 1, 212-218, April 2003
Laboratory of Pharmacology and Chemistry, National Institute of
Environmental Health Sciences, Research Triangle Park, North Carolina
(Y.L., L.Q., G.L., W.Z., B.L., J.-S.H.); and Department of
Bioengineering, Dalian University of Technology, Dalian, China (L.A.)
Inflammation in the brain has increasingly been recognized to play an
important role in the pathogenesis of several neurodegenerative disorders, including Parkinson's disease and Alzheimer's disease. Inflammation-mediated neurodegeneration involves activation of the
brain's resident immune cells, the microglia, which produce proinflammatory and neurotoxic factors, including cytokines, reactive oxygen intermediates, nitric oxide, and eicosanoids that impact on
neurons to induce neurodegeneration. Hence, identification of compounds
that prevent microglial activation may be highly desirable in the
search for therapeutic agents for inflammation-mediated neurodegenerative diseases. In this study, we report that
dextromethorphan (DM), an ingredient widely used in antitussive
remedies, reduced the inflammation-mediated degeneration of
dopaminergic neurons through inhibition of microglial activation.
Pretreatment (30 min) of rat mesencephalic neuron-glia cultures with DM
(1-10 µM) reduced, in a dose-dependent manner, the
microglia-mediated degeneration of dopaminergic neurons induced by
lipopolysaccharide (LPS, 10 ng/ml). Significant neuroprotection by DM
was also evident when DM was applied to cultures up to 60 min after the
addition of LPS. The neuroprotective effect of DM was attributed to
inhibition of LPS-stimulated microglial activation because DM
significantly inhibited the LPS-induced production of tumor necrosis
factor-
, nitric oxide, and superoxide free radicals. This conclusion
was further supported by the finding that DM failed to prevent
1-methyl-4-phenylpyridinium- or 
-amyloid peptide (1-42)-induced
dopaminergic neurotoxicity in neuron-enriched cultures. In addition,
because LPS did not produce any significant increase in the release of
excitatory amino acids from neuron-glia cultures and
N-methyl-D-aspartate antagonist
dizocilpine maleate failed to afford significant neuroprotection, it is
unlikely that the neuroprotective effect of DM is mediated through
N-methyl-D-aspartate receptors. These
results suggest that DM may be a promising therapeutic agent for the
treatment of Parkinson's disease.
This article has been cited by other articles:
|
|
 |
|
  S. Kim, M. Moon, and S. Park Exendin-4 protects dopaminergic neurons by inhibition of microglial activation and matrix metalloproteinase-3 expression in an animal model of Parkinson's disease J. Endocrinol., September 1, 2009; 202(3): 431 - 439. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-T. Shih, I.-J. Chen, Y.-C. Wu, and Y.-C. Lo San-Huang-Xie-Xin-Tang Protects Against Activated Microglia- and 6-OHDA-induced Toxicity in Neuronal SH-SY5Y Cells Evid. Based Complement. Altern. Med., April 1, 2009; (2009) nep025v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-L. Liu, Y.-H. Li, G.-Y. Shi, S.-H. Tang, S.-J. Jiang, C.-W. Huang, P.-Y. Liu, J.-S. Hong, and H.-L. Wu Dextromethorphan reduces oxidative stress and inhibits atherosclerosis and neointima formation in mice Cardiovasc Res, April 1, 2009; 82(1): 161 - 169. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Hayakawa, K. Mishima, M. Nozako, M. Hazekawa, S. Mishima, M. Fujioka, K. Orito, N. Egashira, K. Iwasaki, and M. Fujiwara Delayed Treatment With Minocycline Ameliorates Neurologic Impairment Through Activated Microglia Expressing a High-Mobility Group Box1-Inhibiting Mechanism Stroke, March 1, 2008; 39(3): 951 - 958. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. D. Wahner, J. M. Bronstein, Y. M. Bordelon, and B. Ritz Nonsteroidal anti-inflammatory drugs may protect against Parkinson disease Neurology, November 6, 2007; 69(19): 1836 - 1842. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Qian, K. S. Tan, S.-J. Wei, H.-M. Wu, Z. Xu, B. Wilson, R.-B. Lu, J.-S. Hong, and P. M. Flood Microglia-Mediated Neurotoxicity Is Inhibited by Morphine through an Opioid Receptor-Independent Reduction of NADPH Oxidase Activity J. Immunol., July 15, 2007; 179(2): 1198 - 1209. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Woodard, J. Groden, M. Goodwin, and J. Bodfish A placebo double-blind pilot study of dextromethorphan for problematic behaviors in children with autism Autism, January 1, 2007; 11(1): 29 - 41. [Abstract] [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]
|
|
|
|
|
|
G. Li, G. Cui, N.-S. Tzeng, S.-J. Wei, T. Wang, M. L. Block, and J.-S. Hong Femtomolar concentrations of dextromethorphan protect mesencephalic dopaminergic neurons from inflammatory damage FASEB J, April 1, 2005; 19(6): 489 - 496. [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]
|
|
|
|
 |
|
 R. B. Rock, G. Gekker, S. Hu, W. S. Sheng, M. Cheeran, J. R. Lokensgard, and P. K. Peterson Role of Microglia in Central Nervous System Infections Clin. Microbiol. Rev., October 1, 2004; 17(4): 942 - 964. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
