Related Experiment Video
Updated: Mar 29, 2026
Sub-acute Cerebral Microhemorrhages Induced by Lipopolysaccharide Injection in Rats
Published on: October 17, 2018
Minocycline protects against lipopolysaccharide-induced cognitive impairment in mice
Yue Hou1, Guanbo Xie2,3, Xia Liu1,3
1College of Life and Health Sciences, Northeastern University, 110004, Shenyang, China.
Rationale:
The role of glial cells, especially microglia and astrocytes, in neuroinflammation and cognition has been studied intensively. Lipopolysaccharide (LPS), a commonly used inducer of neuroinflammation, can cause cognitive impairment. Minocycline is known to possess potent neuroprotective activity, but its effect on LPS-induced cognitive impairment is unknown.
Objectives:
This study aims to investigate the effects of minocycline on LPS-induced cognitive impairment and glial cell activation in mice.
Methods:
Behavioral tests were conducted for cognitive function, immunohistochemistry for microglial and astrocyte response, and quantitative PCR for mRNA expression of proinflammatory cytokines.
Results:
Minocycline significantly reversed the decreased spontaneous alternation induced by intrahippocampal administration of LPS in the Y-maze task. In the Morris water maze place navigation test, minocycline decreased the escape latency and distance traveled compared to LPS-treated mice. In the probe test, minocycline-treated mice spent more time in the target quadrant and crossed the platform area more frequently than animals in the LPS-treated group. Minocycline produced a significant decrease in the number of Iba-1- and GFAP-positive hippocampal cells compared to the LPS-treated group. Minocycline-treated mice had significantly reduced hippocampal TNF-α and IL-1β mRNA levels compared with LPS-treated animals. Minocycline caused a significant increase in hippocampal BDNF expression compared to the LPS-treated group.
Conclusions:
Minocycline can attenuate LPS-induced cognitive impairments in mice. This effect may be associated with its action to suppress the activation of microglia and astrocytes and to normalize BDNF expression. Since neuroinflammatory processes and cognitive impairments are implicated in neurodegenerative disorders, minocycline may be a promising candidate for treating such diseases.
Insights
Minocycline treatment reversed lipopolysaccharide (LPS)-induced cognitive deficits in mice by reducing neuroinflammation and normalizing brain-derived neurotrophic factor (BDNF) levels.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Glial cells, including microglia and astrocytes, play key roles in neuroinflammation and cognition.
- Lipopolysaccharide (LPS) is a common neuroinflammation inducer that impairs cognition.
- Minocycline exhibits neuroprotective properties, but its efficacy against LPS-induced cognitive impairment requires investigation.
Purpose of the Study:
- To evaluate minocycline's effects on LPS-induced cognitive impairment in mice.
- To assess minocycline's impact on glial cell activation (microglia and astrocytes) in the context of LPS exposure.
- To examine minocycline's influence on neuroinflammatory markers and BDNF expression.
Main Methods:
- Cognitive function was assessed using behavioral tests, including the Y-maze and Morris water maze.
- Immunohistochemistry was employed to quantify microglial and astrocyte activation in the hippocampus.
- Quantitative PCR was used to measure the mRNA expression of pro-inflammatory cytokines and BDNF.
Main Results:
- Minocycline significantly ameliorated LPS-induced cognitive deficits in spatial memory and working memory tasks.
- Treatment with minocycline markedly reduced the activation of microglia (Iba-1 positive cells) and astrocytes (GFAP positive cells) in the hippocampus.
- Minocycline administration led to decreased expression of pro-inflammatory cytokines (TNF-α, IL-1β) and increased expression of BDNF in the hippocampus.
Conclusions:
- Minocycline effectively attenuates LPS-induced cognitive impairments in mice.
- The neuroprotective effects of minocycline are associated with the suppression of microglial and astrocyte activation and the normalization of BDNF levels.
- Minocycline shows potential as a therapeutic agent for neurodegenerative diseases characterized by neuroinflammation and cognitive decline.
