Bone marrow transplantation reveals roles for brain macrophage/microglia TNF signaling and nitric oxide production in excitotoxic neuronal death

Zhihong Guo, Titilola Iyun, Weiming Fu, Peisu Zhang, Mark P. Mattson

Research output: Contribution to journalArticlepeer-review

Abstract

The signaling mechanisms by which brain macrophages and microglia (BMM) respond to injury and disease, and how their responses affect neurodegenerative processes are largely unknown. Here we show that bone marrow transplantation can be used to introduce genetically modified BMM into the adult mouse brain to reveal the functions of one or more BMM genes in neuronal injury responses. Mice in which endogenous BMM were replaced with cells from mice lacking p55 and p75 tumor necrosis factor (TNF) receptors exhibit increased vulnerability of hippocampal neurons to excitotoxic injury suggesting a role for TNF signaling in BMM in the excitotoxic injury response. Neurons in the brains of mice with BMM lacking nitric oxide synthase exhibit reduced protein nitration and are less vulnerable to excitotoxic damage, indicating a pivotal role for BMM nitric oxide production in excitotoxic neuronal damage.

Original languageEnglish (US)
Pages (from-to)219-234
Number of pages16
JournalNeuroMolecular Medicine
Volume5
Issue number3
DOIs
StatePublished - 2004

Keywords

  • Apoptosis
  • Bone marrow transplantation
  • Excitotoxicity
  • Hippocampus
  • Microglia
  • Tumor necrosis factor

ASJC Scopus subject areas

  • Neuroscience(all)
  • Genetics
  • Cell Biology

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