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Lipopolysaccharide-induced microglial activation induces learning and memory deficits without neuronal cell death in rats
被引:195
作者:
Tanaka, S
Ide, M
Shibutani, T
Ohtaki, H
Numazawa, S
Shioda, S
Yoshida, T
机构:
[1] Showa Univ, Sch Pharmaceut Sci, Dept Biochem Toxicol, Shinagawa Ku, Tokyo 1428555, Japan
[2] Showa Univ, Sch Med, Dept Anat, Tokyo 1428555, Japan
关键词:
lipopolysaccharide;
passive avoidance test;
microglia;
H-3]MK-801;
brain-derived neurotrophic factor;
D O I:
10.1002/jnr.20752
中图分类号:
Q189 [神经科学];
学科分类号:
071006 ;
摘要:
We used lipopolysaccharide (LPS) to activate microglia that play an important role in the brain immune system. LPS injected into the rat hippocampus CA1 region activated microglial cells resulting in an increased production of interleukin (IL)-1 beta and tumor necrosis factor (TNF)-alpha in the hippocampus during the initial stage of treatment. Immunostaining for IL-1 beta was increased at 6 hr after LPS injection. IL-1 beta-immunopositive cells were co-localized with immunostaining for CD11b. Subacute treatment with LPS by the same route for 5 days caused long-term activation of microglia and induced learning and memory deficits in animals when examined with a step-through passive avoidance test, but histochemical analysis showed that neuronal cell death was not observed under these experimental conditions. The increased expression of the heme oxygenase-1 (HO-1) gene, an oxidative stress maker, was observed. However, the genetic expression of brain-derived neurotrophic factor (BDNF) and its receptor, TrkB, decreased during the course of LPS treatment. We found decreases in [H-3]MK801 binding in the hippocampus CA1 region by LPS-treatment for 5 days. The data shows that glutamatergic transmission was attenuated in the LPS-treated rats. These results suggest that long-term activation of microglia induced by LPS results in a decrease of glutamatergic transmission that leads to learning and memory deficits without neuronal cell death. The physiologic significance of these findings is discussed. (C) 2006 Wiley-Liss, Inc.
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页码:557 / 566
页数:10
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