Femtomolar concentrations of dextromethorphan protect mesencephalic dopaminergic neurons from inflammatory damage

Guorong Li, Gang Cui, Nian Ssheng Tzeng, Sung Jen Wei, Tongguang Wang, Michelle Block, Jau Shyong Hong

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

Inflammation in the brain has increasingly been recognized to play an important role in the pathogenesis of several neurodegenerative disorders, including Parkinson's disease (PD). Progress in the search for effective therapeutic strategies that can halt this degenerative process remains limited. We previously showed that micromolar concentrations of dextromethorphan (DM), a major ingredient of widely used antitussive remedies, reduced the inflammation-mediated degeneration of dopaminergic neurons through the inhibition of microglial activation. In this study, we report that femto- and micromolar concentrations of DM (both pre- and post-treatment) showed equal efficacy in protecting lipopolysaccharide (LPS) -induced dopaminergic neuron death in midbrain neuron-glia cultures. Both concentrations of DM decreased LPS-induced release of nitric oxide, tumor necrosis factor-α, prostaglandin E2 and superoxide from microglia in comparable degrees. The important role of superoxide was demonstrated by DM's failure to show a neuroprotective effect in neuron-glia cultures from NADPH oxidase-deficient mice. These results suggest that the neuroprotective effect elicited by femtomolar concentrations of DM is mediated through the inhibition of LPS-induced proinflammatory factors, especially superoxide. These findings suggest a novel therapeutic concept of using "ultra-low" drug concentrations for the intervention of inflammation-related neurodegenerative diseases.

Original languageEnglish (US)
Pages (from-to)489-496
Number of pages8
JournalFASEB Journal
Volume19
Issue number6
DOIs
StatePublished - Apr 2005
Externally publishedYes

Fingerprint

Dextromethorphan
Dopaminergic Neurons
Neurons
neurons
Superoxides
superoxide anion
lipopolysaccharides
Lipopolysaccharides
neuroprotective effect
neurodegenerative diseases
Neuroprotective Agents
Neuroglia
Neurodegenerative Diseases
antitussive agents
inflammation
Neurodegenerative diseases
Antitussive Agents
Inflammation
therapeutics
tumor necrosis factors

Keywords

  • DM
  • Femtomolar
  • Inflammation
  • Microglia
  • Neuroprotection
  • Parkinson's disease

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Femtomolar concentrations of dextromethorphan protect mesencephalic dopaminergic neurons from inflammatory damage. / Li, Guorong; Cui, Gang; Tzeng, Nian Ssheng; Wei, Sung Jen; Wang, Tongguang; Block, Michelle; Hong, Jau Shyong.

In: FASEB Journal, Vol. 19, No. 6, 04.2005, p. 489-496.

Research output: Contribution to journalArticle

Li, Guorong ; Cui, Gang ; Tzeng, Nian Ssheng ; Wei, Sung Jen ; Wang, Tongguang ; Block, Michelle ; Hong, Jau Shyong. / Femtomolar concentrations of dextromethorphan protect mesencephalic dopaminergic neurons from inflammatory damage. In: FASEB Journal. 2005 ; Vol. 19, No. 6. pp. 489-496.
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