Related Experiment Video
Updated: May 13, 2026
Mitochondrial Preparation from Microglia for Glycan Analysis
Published on: May 30, 2025
Galectin-3 in microglia mediates neuroinflammation-induced cognitive dysfunction via selective elimination of
Hai-Peng Wu1, Xiao-Yi Hu1, Kai Liu1
1Department of Anesthesiology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Abstract:
Microglia-mediated neuroinflammation is increasingly recognized as a contributor to neurodegenerative disease progression. However, how microglia contribute to neuroinflammation-induced cognitive dysfunction remains unclear. Galectin-3 (Gal-3) is a microglia-enriched lectin that regulates inflammatory signaling and phagocytosis, a plausible mediator linking neuroinflammation to cognitive dysfunction. In a lipopolysaccharide (LPS)-induced mouse model of neuroinflammation (0.5 mg/kg for 7 consecutive days), cognitive function was evaluated using the open field, Y-maze, and novel object recognition tests. In vivo CA1 extracellular electrophysiological recordings were used to analyze local field potentials (LFPs) and single-unit spiking activity. Dendritic morphology was evaluated by Golgi staining, and synaptic markers were quantified by immunofluorescence. In hippocampal CA1, microglia exhibited increased Gal-3 expression, enhanced phagocytic activity, and selectively increased engulfment of excitatory synapses. Systemic pharmacologic inhibition with TD139 and microglia-targeted Lgals3 knockdown (AAV-shLgals3 in Cx3cr1-CreERT2 mice) preserved excitatory synapses, restored CA1 gamma power, and improved cognitive performance in the neuroinflammation model. These results identify Gal-3-dependent microglial phagocytosis as a key mechanism linking neuroinflammation to cognitive dysfunction.
Insights
Microglia-driven neuroinflammation impairs cognition. Galectin-3 (Gal-3) on microglia drives this by engulfing synapses, but inhibiting Gal-3 rescues cognitive function in a mouse model.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Neuroinflammation, particularly microglia-mediated, is a key factor in neurodegenerative diseases.
- The precise mechanisms by which microglia contribute to cognitive deficits in neuroinflammation are not fully understood.
- Galectin-3 (Gal-3), a lectin abundant in microglia, influences inflammatory responses and phagocytosis, suggesting a role in linking neuroinflammation to cognitive decline.
Purpose of the Study:
- To investigate the role of Galectin-3 (Gal-3) in microglia-mediated neuroinflammation and subsequent cognitive dysfunction.
- To elucidate the impact of Gal-3 on microglial phagocytosis of synapses in the hippocampus during neuroinflammation.
- To evaluate the therapeutic potential of targeting Gal-3 to mitigate neuroinflammation-induced cognitive deficits.
Main Methods:
- Established a lipopolysaccharide (LPS)-induced mouse model of neuroinflammation.
- Assessed cognitive function using behavioral tests (open field, Y-maze, novel object recognition).
- Analyzed hippocampal CA1 electrophysiology, dendritic morphology (Golgi staining), and synaptic markers (immunofluorescence).
- Utilized systemic Gal-3 inhibition (TD139) and microglia-specific Lgals3 knockdown (AAV-shLgals3).
Main Results:
- LPS-induced neuroinflammation increased microglial Gal-3 expression and phagocytic activity in the hippocampal CA1 region.
- Microglia selectively engulfed excitatory synapses, leading to their loss.
- Pharmacologic inhibition of Gal-3 (TD139) and Lgals3 knockdown preserved synapses, restored hippocampal CA1 gamma power, and improved cognitive performance.
Conclusions:
- Galectin-3 (Gal-3) mediates microglial phagocytosis of excitatory synapses during neuroinflammation.
- Gal-3-dependent microglial phagocytosis is a critical mechanism linking neuroinflammation to cognitive dysfunction.
- Targeting Gal-3 presents a potential therapeutic strategy for neurodegenerative diseases characterized by neuroinflammation and cognitive impairment.
