TNF-α receptor 1 deficiency enhances kainic acid-induced hippocampal injury in mice

Ming Ou Lu, Xing Mei Zhang, Eilhard Mix, Hernan Concha Quezada, Tao Jin, Jie Zhu, Abdu Adem

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

Abstract

The exact role of TNF-α in excitotoxic neurodegeneration of the brain is unclear. To address this issue, the kainic acid (KA)-induced hippocampal injury model, a well-characterized model of human neurodegenerative diseases, was used in TNF-α receptor 1 (TNFR1)-knockout (TNFR1-/-) mice in the present study. After nasal application of a single dose of 40 mg of KA per kilogram body weight, TNFR1-/- mice showed significantly more severe seizures than the wild-type mice. In addition, obvious neurodegeneration, enhanced microglia activation, and astrogliosis in the hippocampus, as well as increased locomotor activity, were found in TNFR1-/- mice compared with the wild-type controls 8 days after KA delivery. Moreover, CC chemokine receptor 3 expression on activated microglia was increased 3 days after KA treatment in TNFR1-/- mice, as measured by flow cytometry. These data suggest that TNF-α may play a protective role through TNFR1 signaling.

Original languageEnglish
Pages (from-to)1608-1614
Number of pages7
JournalJournal of Neuroscience Research
Volume86
Issue number7
DOIs
Publication statusPublished - May 15 2008

Keywords

  • Hippocampus
  • Kainic acid
  • Neurodegeneration
  • TNF-α
  • TNF-α receptor 1 deficiency

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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