Abstract
Through their capacity to secrete, upon activation, a variety of bioactive molecules, brain macrophages (and resident microglia) play an important role in brain immune and inflammatory responses. To test our hypothesis that activated macrophages induce neuronal injury by enhancing neuronal outward K+ current, we studied the effects of lipopolysaccharide (LPS)-stimulated human monocyte-derived macrophage (MDM) on neuronal transient A-type K+ current (IA) and resultant neuronal injury in primary rat hippocampal neuronal cultures. Bath application of LPS-stimulated MDM-conditioned media (MCM+) enhanced neuronal IA in a concentration-dependent manner. Non-stimulated MCM (MCM-) failed to alter IA. The enhancement of neuronal IA was recapitulated in neurons co-cultured with macrophages. The link of MCM(+)-induced enhancement of IA to MCM(+)-associated neuronal injury, as detected by propidium iodide and 4″,6-diamidino-2-phenylindol staining (DAPI) and 3-(4,5-dimethylthiazol-2- yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, was demonstrated by experimental results showing that addition of IA blocker 4-aminopyridine to the cultures protected hippocampal neurons from MCM(+)-induced neuronal injury. Further investigation revealed that glutamate was involved in MCM(+)-induced enhancement of neuronal IA. These results suggest that during brain inflammation macrophages (and microglia) might mediate neuronal injury via enhancement of neuronal IA, and that neuronal Kv channel might be a potential target for the development of therapeutic strategies for some neurodegenerative disorders by which immune and inflammatory responses are believed to be involved in the pathogenesis.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 214-222 |
| Number of pages | 9 |
| Journal | European Journal of Neuroscience |
| Volume | 31 |
| Issue number | 2 |
| DOIs | |
| State | Published - Jan 1 2010 |
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Keywords
- Apoptosis
- Glutamate
- Hippocampus
- Neuroinflammation
- Potassium channels
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
Involvement of the 4-aminopyridine-sensitive transient A-type K+ current in macrophage-induced neuronal injury. / Hu, Dehui; Liu, Jianuo; Keblesh, James; Xiong, Huangui.
In: European Journal of Neuroscience, Vol. 31, No. 2, 01.01.2010, p. 214-222.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Involvement of the 4-aminopyridine-sensitive transient A-type K+ current in macrophage-induced neuronal injury
AU - Hu, Dehui
AU - Liu, Jianuo
AU - Keblesh, James
AU - Xiong, Huangui
PY - 2010/1/1
Y1 - 2010/1/1
N2 - Through their capacity to secrete, upon activation, a variety of bioactive molecules, brain macrophages (and resident microglia) play an important role in brain immune and inflammatory responses. To test our hypothesis that activated macrophages induce neuronal injury by enhancing neuronal outward K+ current, we studied the effects of lipopolysaccharide (LPS)-stimulated human monocyte-derived macrophage (MDM) on neuronal transient A-type K+ current (IA) and resultant neuronal injury in primary rat hippocampal neuronal cultures. Bath application of LPS-stimulated MDM-conditioned media (MCM+) enhanced neuronal IA in a concentration-dependent manner. Non-stimulated MCM (MCM-) failed to alter IA. The enhancement of neuronal IA was recapitulated in neurons co-cultured with macrophages. The link of MCM(+)-induced enhancement of IA to MCM(+)-associated neuronal injury, as detected by propidium iodide and 4″,6-diamidino-2-phenylindol staining (DAPI) and 3-(4,5-dimethylthiazol-2- yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, was demonstrated by experimental results showing that addition of IA blocker 4-aminopyridine to the cultures protected hippocampal neurons from MCM(+)-induced neuronal injury. Further investigation revealed that glutamate was involved in MCM(+)-induced enhancement of neuronal IA. These results suggest that during brain inflammation macrophages (and microglia) might mediate neuronal injury via enhancement of neuronal IA, and that neuronal Kv channel might be a potential target for the development of therapeutic strategies for some neurodegenerative disorders by which immune and inflammatory responses are believed to be involved in the pathogenesis.
AB - Through their capacity to secrete, upon activation, a variety of bioactive molecules, brain macrophages (and resident microglia) play an important role in brain immune and inflammatory responses. To test our hypothesis that activated macrophages induce neuronal injury by enhancing neuronal outward K+ current, we studied the effects of lipopolysaccharide (LPS)-stimulated human monocyte-derived macrophage (MDM) on neuronal transient A-type K+ current (IA) and resultant neuronal injury in primary rat hippocampal neuronal cultures. Bath application of LPS-stimulated MDM-conditioned media (MCM+) enhanced neuronal IA in a concentration-dependent manner. Non-stimulated MCM (MCM-) failed to alter IA. The enhancement of neuronal IA was recapitulated in neurons co-cultured with macrophages. The link of MCM(+)-induced enhancement of IA to MCM(+)-associated neuronal injury, as detected by propidium iodide and 4″,6-diamidino-2-phenylindol staining (DAPI) and 3-(4,5-dimethylthiazol-2- yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, was demonstrated by experimental results showing that addition of IA blocker 4-aminopyridine to the cultures protected hippocampal neurons from MCM(+)-induced neuronal injury. Further investigation revealed that glutamate was involved in MCM(+)-induced enhancement of neuronal IA. These results suggest that during brain inflammation macrophages (and microglia) might mediate neuronal injury via enhancement of neuronal IA, and that neuronal Kv channel might be a potential target for the development of therapeutic strategies for some neurodegenerative disorders by which immune and inflammatory responses are believed to be involved in the pathogenesis.
KW - Apoptosis
KW - Glutamate
KW - Hippocampus
KW - Neuroinflammation
KW - Potassium channels
UR - http://www.scopus.com/inward/record.url?scp=74549224543&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=74549224543&partnerID=8YFLogxK
U2 - 10.1111/j.1460-9568.2009.07063.x
DO - 10.1111/j.1460-9568.2009.07063.x
M3 - Article
VL - 31
SP - 214
EP - 222
JO - European Journal of Neuroscience
JF - European Journal of Neuroscience
SN - 0953-816X
IS - 2
ER -