Minocycline protects neurons against glial cells-mediated bilirubin neurotoxicity

Changwei Zhou, Rong Sun, Chongyi Sun, Minghao Gu, Chuan Guo, Jiyan Zhang, Yansheng Du, Huiying Gu, Qingpeng Liu

Research output: Contribution to journalArticle

Abstract

Unconjugated bilirubin, the end product of heme catabolism and antioxidant, induced brain damage in human neonates is a well-recognized clinical syndrome. However, the cellular and molecular mechanisms underlying bilirubin neurotoxicity remain unclear. To characterize the sequence of events leading to bilirubin-induced neurotoxicity, we investigated whether bilirubin-induced glial activation was involved in bilirubin neurotoxicity by exposing co-cultured rat glial cells and cerebellar granule neurons (CGN) to bilirubin. We found that bilirubin could markedly induce the expression of TNF-α and iNOS in glial cells, and even at low concentrations, the co-culture of glial cells with neurons significantly enhances neurotoxicity of bilirubin. Pretreatment of the co-cultured cells with minocycline protected CGN from glia-mediated bilirubin neurotoxicity and inhibited overexpression of TNF-α and iNOS in glia. Furthermore, we found that high doses of bilirubin were able to induce glial injury, and minocycline attenuated bilirubin-induced glial cell death. Our data suggest that glial cells play an important role in brain damage caused by bilirubin, and minocycline blocks bilirubin-induced encephalopathy possibly by directly and indirectly inhibiting neuronal death pathways.

Original languageEnglish (US)
Pages (from-to)102-105
Number of pages4
JournalBrain Research Bulletin
Volume154
DOIs
StatePublished - Jan 2020

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Minocycline
Bilirubin
Neuroglia
Neurons
Kernicterus
Brain
Coculture Techniques
Heme
Cultured Cells
Cell Death
Antioxidants

Keywords

  • Bilirubin
  • Glia
  • Minocycline
  • Neuroprotection
  • Neurotoxicity

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Minocycline protects neurons against glial cells-mediated bilirubin neurotoxicity. / Zhou, Changwei; Sun, Rong; Sun, Chongyi; Gu, Minghao; Guo, Chuan; Zhang, Jiyan; Du, Yansheng; Gu, Huiying; Liu, Qingpeng.

In: Brain Research Bulletin, Vol. 154, 01.2020, p. 102-105.

Research output: Contribution to journalArticle

Zhou, Changwei ; Sun, Rong ; Sun, Chongyi ; Gu, Minghao ; Guo, Chuan ; Zhang, Jiyan ; Du, Yansheng ; Gu, Huiying ; Liu, Qingpeng. / Minocycline protects neurons against glial cells-mediated bilirubin neurotoxicity. In: Brain Research Bulletin. 2020 ; Vol. 154. pp. 102-105.
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