Bone marrow transplantation reveals roles for brain macrophage/microglia TNF signaling and nitric oxide production in excitotoxic neuronal death.
Neuromolecular Med
; 5(3): 219-34, 2004.
Article
in En
| MEDLINE
| ID: mdl-15626822
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.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Tumor Necrosis Factor-alpha
/
Microglia
/
Macrophages
/
Nerve Degeneration
/
Neurotoxins
/
Nitric Oxide
Limits:
Animals
Language:
En
Journal:
Neuromolecular Med
Journal subject:
BIOLOGIA MOLECULAR
/
NEUROLOGIA
Year:
2004
Document type:
Article
Affiliation country:
United States