RRC ID 12037
著者 Tanaka S, Ide M, Shibutani T, Ohtaki H, Numazawa S, Shioda S, Yoshida T.
タイトル Lipopolysaccharide-induced microglial activation induces learning and memory deficits without neuronal cell death in rats.
ジャーナル J Neurosci Res
Abstract 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)-1beta and tumor necrosis factor (TNF)-alpha in the hippocampus during the initial stage of treatment. Immunostaining for IL-1beta was increased at 6 hr after LPS injection. IL-1beta-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 [3H]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.
巻・号 83(4)
ページ 557-66
公開日 2006-3-1
DOI 10.1002/jnr.20752
PMID 16429444
MeSH Animals Avoidance Learning Blotting, Northern Brain-Derived Neurotrophic Factor / metabolism Cell Death / drug effects Dizocilpine Maleate / metabolism Excitatory Amino Acid Antagonists / metabolism Heme Oxygenase-1 / metabolism Hippocampus / pathology Immunohistochemistry In Situ Nick-End Labeling Interleukin-1 / metabolism Learning Disabilities / chemically induced* Learning Disabilities / pathology Lipopolysaccharides / pharmacology* Memory Disorders / chemically induced* Memory Disorders / pathology Microglia / drug effects* Motor Activity / drug effects Neurons / drug effects* Psychomotor Performance / drug effects Rats Receptor, trkB / drug effects Receptor, trkB / metabolism Tumor Necrosis Factor-alpha / metabolism
IF 4.699
引用数 152
WOS 分野 NEUROSCIENCES
リソース情報
遺伝子材料 pRHO1 Rat heme oxygenase cDNA (RDB1208)