Lipopolysaccharide extends the lifespan of mouse primary-cultured microglia.
Microglial activation has been implicated in the recognition and phagocytic removal of degenerating neurons; however, this process must be tightly regulated in the central nervous system, because prolonged activation could damage normal neurons. We report that mouse primary-cultured microglia, which are destined to die within a few days under ordinary culture conditions, can live for more than 1 month when kept activated by lipopolysaccharide (LPS) treatment. Primary-cultured microglia treated with sublethal doses of LPS remained viable, without any measurable increase in apoptotic or necrotic cell death. LPS-treated microglia had an arborescent shape, with enlarged somata and thickened cell bodies. Although the amount of intracellular ATP in these microglia was reduced by 2 h after the start of LPS treatment, this had no effect on the viability of the cells. LPS treatment of microglia increased the antiapoptotic factor Bcl-xL protein level at day 1, although the level of the proapoptotic Bcl-associated X-protein was unaffected. Furthermore, the level of microtubule-associated light chain 3, a marker protein for autophagy, decreased at 3 h after exposure to LPS. These data show that the optimal dose of LPS suppresses the induction of both apoptosis and autophagy in primary-cultured microglia, allowing the cells to stay alive for more than 1 month. Because long-lived microglia may play critical roles in the exacerbation of neurodegeneration, our findings suggest that inducing a resting stage in active microglia could be a new and promising strategy to inhibit the deterioration of neurodegenerative disease.
Department of Physiology, Fujita Health University School of Medicine, Kutsukake-cho, Toyoake, Japan.
Yoko S
YS
Kaneko
Akira
A
Nakashima
Keiji
K
Mori
Toshiharu
T
Nagatsu
Ikuko
I
Nagatsu
Akira
A
Ota
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000166:cytology / Q000187:drug effects*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009336:Necrosis / Q000188:drug therapy; D018696:Neuroprotective Agents / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
C494812:Bcl2l1 protein, mouse; D008070:Lipopolysaccharides; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D000255:Adenosine Triphosphate; C505409:Casp3 protein, mouse; D053148:Caspase 3