Lipopolysaccharide extends the lifespan of mouse primary-cultured microglia

• Published in: Brain research Vol. 1279; pp. 9 - 20
• Main Authors: Kaneko, Yoko S, Nakashima, Akira, Mori, Keiji, Nagatsu, Toshiharu, Nagatsu, Ikuko, Ota, Akira
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 07.07.2009; Elsevier
• Subjects: Adenosine Triphosphate - metabolism; Animals; Apoptosis; Apoptosis - drug effects; Autophagy; bcl-2-Associated X Protein - metabolism; bcl-X Protein - metabolism; Biological and medical sciences; Caspase 3 - metabolism; Cell Survival - drug effects; Cells, Cultured; Fundamental and applied biological sciences. Psychology; Isolated neuron and nerve. Neuroglia; Lipopolysaccharide; Lipopolysaccharides - pharmacology; Mice; Mice, Inbred C57BL; Microglia; Microglia - cytology; Microglia - drug effects; Microtubule-Associated Proteins - metabolism; Necrosis - drug therapy; Neurology; Neuroprotective Agents - pharmacology; RNA, Messenger - metabolism; Vertebrates: nervous system and sense organs; microtubule-associated light chain 3; CNS; hypoxanthine guanine phosphoribosyl transferase 1; Autophagy; LPS; phosphate-buffered saline containing 0.05% Tween 20; complementary DNA; SD; analysis of variance; minimum essential medium; ANOVA; reactive oxygen species; PGC-1; cDNA; SN; LC3; Bcl-associated X-protein; polymerase chain reaction; substantia nigra; central nervous system; Microglia; peroxisome proliferator-activated receptorγ coactivator 1; MEM; PBST; ROS; BAX; HPRT1; lipopolysaccharide; PCR; standard deviation; Apoptosis; Lipopolysaccharide; Cell culture; Vertebrata; Mammalia; Mouse; Cell death; Neuroglia; Animal; Rodentia
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2009.05.008

Abstract 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.