Minocycline blocks bilirubin neurotoxicity and prevents hyperbilirubinemia-induced cerebellar hypoplasia in the Gunn rat

Suizhen Lin, Xing Wei, Kelly R. Bales, Aaron B C Paul, Zhizhong Ma, Guangmei Yan, Steven M. Paul, Yansheng Du

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Encephalopathy induced by hyperbilirubinemia in infants has been described in the medical literature for over a century but neither the cellular nor molecular mechanisms underlying bilirubin neurotoxicity are well understood. In this study, we have demonstrated that minocycline potently protects primary cultured rat cerebellar granule neurons against bilirubin neurotoxicity (IC 50 ≈ 2 μM) and almost completely blocks cerebellar hypoplasia and the profound loss of Purkinje and granule neurons observed in homozygous Gunn rats, a genetic model of hyperbilirubinemia-induced neurotoxicity. Minocycline-treated newborn Gunn rats had nearly equivalent numbers of viable Purkinje and granule neurons in the cerebellum as did control animals. Moreover, minocycline inhibits the bilirubin-induced phosphorylation of p38 mitogen-activated protein kinase both in vivo as well as in vitro. Taken together our data demonstrate that minocycline is able to greatly reduce bilirubin-induced neurotoxicity and suggest that minocycline's neuroprotective effects may be due in part to an inhibition of p38 mitogen-activated protein kinase activity. Our findings may lead to novel approaches for treating bilirubin-induced encephalopathy.

Original languageEnglish
Pages (from-to)21-27
Number of pages7
JournalEuropean Journal of Neuroscience
Volume22
Issue number1
DOIs
StatePublished - Jul 2005

Fingerprint

Gunn Rats
Minocycline
Hyperbilirubinemia
Bilirubin
Purkinje Cells
p38 Mitogen-Activated Protein Kinases
Kernicterus
Genetic Models
Brain Diseases
Neuroprotective Agents
Cerebellum
Phosphorylation
Cerebellar Hypoplasia
Neurons

Keywords

  • Apoptosis
  • Granule neurons
  • Minocycline
  • p38 mitogen-activated protein kinase

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Minocycline blocks bilirubin neurotoxicity and prevents hyperbilirubinemia-induced cerebellar hypoplasia in the Gunn rat. / Lin, Suizhen; Wei, Xing; Bales, Kelly R.; Paul, Aaron B C; Ma, Zhizhong; Yan, Guangmei; Paul, Steven M.; Du, Yansheng.

In: European Journal of Neuroscience, Vol. 22, No. 1, 07.2005, p. 21-27.

Research output: Contribution to journalArticle

Lin, Suizhen ; Wei, Xing ; Bales, Kelly R. ; Paul, Aaron B C ; Ma, Zhizhong ; Yan, Guangmei ; Paul, Steven M. ; Du, Yansheng. / Minocycline blocks bilirubin neurotoxicity and prevents hyperbilirubinemia-induced cerebellar hypoplasia in the Gunn rat. In: European Journal of Neuroscience. 2005 ; Vol. 22, No. 1. pp. 21-27.
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