Lipopolysaccharide-Induced Depression in Obesity

Investigation of microglial synaptic elimination and neuroinflammation mechanisms underlying depression in obesity

Overview

This neuroscience research investigated how lipopolysaccharide (LPS) exacerbates depressive-like behaviors in obese rats through complement C1q-mediated synaptic elimination by microglia. The study explored the combined effects of high-fat diet (HFD) consumption and LPS administration on microglial dysfunction, synaptic loss, and behavioral outcomes, revealing critical insights into obesity-related mental health complications.

Problem

Prolonged high-fat diet consumption impairs cognition and increases depression risk, but the mechanisms by which metabolic disturbances trigger neuroinflammation and synaptic loss remained poorly understood. The combined effects of obesity and inflammatory challenges on microglial function and mental health outcomes needed thorough investigation.

Solution

Conducted comprehensive animal model study using 64 male Wistar rats fed either normal diet or HFD for 12 weeks, followed by LPS administration. Performed multi-modal analysis including behavioral assessments, western blot analysis, qRT-PCR, immunofluorescence staining, and brain metabolome determination to characterize the neuroinflammatory cascade and synaptic changes.

Impact

• •Published in Acta Physiologica (Wiley) - High-impact neuroscience journal
• •Demonstrated LPS aggravates metabolic disturbances and neuroinflammation in obese models
• •Identified C1q-mediated microglial synaptic engulfment as key mechanism
• •Revealed exacerbated depressive-like behaviors in combined HFD + LPS conditions
• •Established blood-brain barrier disruption and decreased neurogenesis in obesity
• •Characterized inflammatory gene expression patterns in microglia and astrocytes

Key Skills Applied