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Lipopolysaccharide‐induced microglial activation induces learning and memory deficits without neuronal cell deathin rats
Author(s) -
Tanaka Sachiko,
Ide Masatoshi,
Shibutani Toshiomi,
Ohtaki Hirokazu,
Numazawa Satoshi,
Shioda Seiji,
Yoshida Takemi
Publication year - 2006
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.20752
Subject(s) - microglia , hippocampus , glutamatergic , lipopolysaccharide , neurotrophic factors , immunostaining , tumor necrosis factor alpha , tlr4 , integrin alpha m , glutamate receptor , endocrinology , nmda receptor , brain derived neurotrophic factor , neuroscience , medicine , biology , chemistry , receptor , inflammation , immunohistochemistry
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)‐1β and tumor necrosis factor (TNF)‐α in the hippocampus during the initial stage of treatment. Immunostaining for IL‐1β was increased at 6 hr after LPS injection. IL‐1β‐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 [ 3 H]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. © 2006 Wiley‐Liss, Inc.