Microglial activation in neuroinflammation: implications for the etiology of neurodegeneration.
BACKGROUND
Activated microglia secrete inflammatory cytokines and may play roles in the progression of neurodegenerative diseases. However, the mechanism underlying microglial activation remains unclear.


OBJECTIVE
Our aim was to examine the regulation of activated microglia through their cell death and survival pathways.


METHODS
We used mouse primary-cultured microglia, which are destined to die within a few days under ordinary culture conditions. The microglia live for longer than 1 month, without any measurable increase in apoptotic or necrotic cell death, when kept activated by sublethal concentrations of lipopolysaccharide (LPS).


RESULTS
LPS-treated microglia showed changes in shape. LPS treatment had no effect on the level of the proapoptotic Bcl-2-associated X protein but increased the level of the antiapoptotic protein Bcl-xL at day 1. Furthermore, the level of microtubule-associated light chain 3-II, a marker protein for autophagy, was decreased 3 h after exposure to LPS.


CONCLUSIONS
An increase in Bcl-xL seems to inhibit both apoptosis and autophagy. Our results suggest that long-lived microglia resulting from exposure to the optimal dose of LPS may play critical roles in the progression of neurodegeneration.
Department of Physiology, Fujita Health University School of Medicine, Toyoake, Japan.
Yoko S
YS
Kaneko
Akira
A
Nakashima
Keiji
K
Mori
Toshiharu
T
Nagatsu
Ikuko
I
Nagatsu
Akira
A
Ota
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000166:cytology; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D017628:Microglia / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
D016207:Cytokines; D008070:Lipopolysaccharides; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D053148:Caspase 3