Premium
Norepinephrine protects cortical neurons against microglial‐induced cell death
Author(s) -
Madrigal Jose L.M.,
Feinstein Douglas L.,
Russo Cinzia Dello
Publication year - 2005
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.20481
Subject(s) - microglia , neuroprotection , neurotoxicity , programmed cell death , lipopolysaccharide , nitric oxide synthase , downregulation and upregulation , nitric oxide , neuroinflammation , biology , neuron , neuroscience , microbiology and biotechnology , inflammation , apoptosis , endocrinology , medicine , immunology , biochemistry , toxicity , gene
Interleukin‐1 beta (IL‐1β) is one of the main cytokines involved in the inflammatory response; it has multiple effects that can contribute to cell damage, one of which is the upregulation of the inducible form of nitric oxide (NO) synthase (NOS2) in certain cell types. We demonstrated previously that in vivo, cortical microglial inflammatory responses were increased when noradrenaline (NE) levels were depleted, suggesting that NE can reduce microglial activation. In the present report, we examined the role of IL‐1β in neurotoxicity induced by microglial‐conditioned media, and possible neuroprotective effects of NE. Incubation of cortical neurons with conditioned media (CM) obtained from lipopolysaccharide (LPS)‐treated microglia induced neuronal NOS2 expression and increased neuronal cell death, and these responses were reduced if the neurons were coincubated with interleukin‐1 receptor antagonist. Cotreatment of microglial cells with LPS plus NE potently blocked IL‐1β production and reduced the ability of the CM to induce neuronal NOS2 and cell death. These results suggest that microglial release of IL‐1β is an important activator of neuronal inflammatory responses, and that protective effects of NE upon neurons involve a reduction of microglial‐derived IL‐1β. © 2005 Wiley‐Liss, Inc.