Microglial Activation Plays a Critical Role in LPS-Induced Contextual Fear Memory Consolidation Impairment and Blood-Brain Barrier Disruption.

BACKGROUND: Accurately predicting environmental dangers is a fundamental ability for animal and human survival. Fear memory could be disrupted by various stimuli, including inflammation, which can be mimicked by lipopolysaccharide (LPS) injection. LPS, which can activate microglia and disrupt the blood-brain barrier (BBB), can impair contextual fear memory consolidation when injected immediately after fear conditioning. However, the mechanism is not clear. Minocycline, a tetracycline derivative, can reduce inflammation and microglial activation. This study aims to explore the role of microglial activation in LPS-induced contextual fear memory consolidation impairment and BBB disruption. METHODS: Immediately after the fear conditioning training, 0.5 or 1 mg/kg LPS was injected i.p., and the contextual fear memory was tested 24 h later, followed by biochemical and histological test. RESULTS: The results showed that LPS impaired contextual fear memory consolidation, which was accompanied by a significant leakage of immunoglobulin G (IgG) in the hippocampus 24 h after LPS treatment. In addition, significantly decreased levels of claudin-5 and occludin, and significantly upregulated levels of caveolin-1, microglial activation, and the levels of pro-inflammatory factors interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were found in the hippocampus. In contrast, minocycline, which could inhibit microglial activation, reduce LPS-induced memory impairment and BBB damage. CONCLUSIONS: In summary, the study provides preliminary evidence that LPS can impair the consolidation of contextual fear memory by causing microglial activation, releasing pro-inflammatory factors IL-1β and TNF-α, and leading to BBB disruption in the hippocampus of mice.