Lipopolysaccharide-induced microglial activation induces learning and memory deficits without neuronal cell deathin rats
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.
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LPS induces production of TNF-α in the brain by microglial cells, which promotes BBB dysfunction and also causes neuronal cell death by phagocytosis.
“On the other hand, it has been shown that LPS induces the production of TNF-α in the brain by microglial cells, which promotes BBB dysfunction and also causes neuronal cell death by phagocytosis (Tanaka et al., 2006; Nishioku et al., 2010; Smith et al., 2012; Neniskyte et al., 2014).”
From The impact of microglial activation on blood-brain barrier in brain diseases (2014) · cites this paper as Tanaka et al., 2006
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- Authors
- Tanaka, S., Ide, M., Shibutani, T., Ohtaki, H., Numazawa, S., Shioda, S., & Yoshida, T.
- Affiliations
- SHOWA Medical University (JP)
- Corresponding author
- Tanaka, Sachiko
- Venue
- Journal of Neuroscience Research
- Publisher
- Wiley
- Published
- 2006
- Volume
- 83
- Issue
- 4
- Pages
- 557-566
- ISSN
- 0360-4012 (ISSN-L)
- 1097-4547
- OpenAlex
- W2052783666
- Cited by
- 224
- References
- 62
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 4 · 2023: 15 · 2022: 7 · 2021: 10 · 2020: 14 · 2019: 12 · 2018: 9 · 2017: 11 · 2016: 7 · 2015: 9 · 2014: 13 · 2013: 18 · 2012: 21
- FWCI
- 7.68
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuroscience Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- lipopolysaccharide, microglial activation, learning and memory impairment, hippocampal CA1, IL-1β, TNF-α, CD11b, heme oxygenase-1, oxidative stress, brain-derived neurotrophic factor, TrkB receptor, glutamatergic neurotransmission, neuroinflammation, neuroprotection
- MeSH terms
- Animals, Avoidance Learning, Hippocampus, Immunohistochemistry, Interleukin-1, Learning Disabilities, Lipopolysaccharides, Memory Disorders, Motor Activity, Neurons, Psychomotor Performance, Tumor Necrosis Factor-alpha, Blotting, Northern, Dizocilpine Maleate, Cell Death, Microglia, Excitatory Amino Acid Antagonists, Brain-Derived Neurotrophic Factor, In Situ Nick-End Labeling, Receptor, trkB, Rats, Heme Oxygenase-1
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