Inhibition of glial inflammatory activation and neurotoxicity by tricyclic antidepressants

Jaegyu Hwang, Long Tai Zheng, Jiyeon Ock, Maan Gee Lee, Sang Hyun Kim, Ho Won Lee, Won Ha Lee, Hae Chul Park, Kyoungho Suk

Research output: Contribution to journalArticle

133 Citations (Scopus)

Abstract

Glial activation and neuroinflammatory processes play an important role in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and HIV dementia. Activated glial cells can secrete various proinflammatory cytokines and neurotoxic mediators, which may contribute to neuronal cell death. Inhibition of glial activation may alleviate neurodegeneration under these conditions. In the present study, the antiinflammatory and neuroprotective effects of tricyclic antidepressants were investigated using cultured brain cells as a model. The results showed that clomipramine and imipramine significantly decreased the production of nitric oxide or tumor necrosis factor-alpha (TNF-α) in microglia and astrocyte cultures. Clomipramine and imipramine also attenuated the expression of inducible nitric oxide synthase and proinflammatory cytokines such as interleukin-1β and TNF-α at mRNA levels. In addition, clomipramine and imipramine inhibited IκB degradation, nuclear translocation of the p65 subunit of NF-κB, and phosphorylation of p38 mitogen-activated protein kinase in the lipopolysaccharide-stimulated microglia cells. Moreover, clomipramine and imipramine were neuroprotective as the drugs reduced microglia-mediated neuroblastoma cell death in a microglia/neuron co-culture. Therefore, these results imply that clomipramine and imipramine have antiinflammatory and neuroprotective effects in the central nervous system by modulating glial activation.

Original languageEnglish
Pages (from-to)826-834
Number of pages9
JournalNeuropharmacology
Volume55
Issue number5
DOIs
Publication statusPublished - 2008 Oct

Keywords

  • Antidepressant
  • Astrocyte
  • Inflammation
  • Microglia
  • Neuroprotection

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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  • Cite this

    Hwang, J., Zheng, L. T., Ock, J., Lee, M. G., Kim, S. H., Lee, H. W., Lee, W. H., Park, H. C., & Suk, K. (2008). Inhibition of glial inflammatory activation and neurotoxicity by tricyclic antidepressants. Neuropharmacology, 55(5), 826-834. https://doi.org/10.1016/j.neuropharm.2008.06.045