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) |