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Updated: Jan 8, 2026
Mouse Footpad Inoculation Model to Study Viral-Induced Neuroinflammatory Responses
Published on: June 14, 2020
Basic Science and Pathogenesis
1University of Dundee, Dundee, Angus, United Kingdom.
Background:
Chronic inflammatory microglia is a key pathological hallmark of Alzheimer's Disease (AD) requiring high metabolic demand. Glucose is a key metabolite vital for microglia responses, and sustained hyperglycaemia is a significant risk for AD development. Understanding how microglia fuel their inflammatory responses is key to understanding how to modulate their behaviour in neurodegenerative diseases.
Method:
Microglia were isolated from APP-NL-G-F mice at different key time points in disease progression (1, 3 and 6 months, n = 4-6 per time point) and interrogated using mass spectrometry and proteomic analysis.
Result:
Proteomic analysis revealed by microglia massively upregulate their glycolysis machinery at 6 months coinciding with significant increases in inflammatory and disease associated protein expression. Interestingly, expression of glucose receptors were significantly decreased, yet increases in proteins involved in glycogen breakdown were increased. Acute (24hr) depletion of glucose in vitro also had no effect on microglia inflammatory responses to lipopolysaccharide (LPS) and glycolysis was maintained, yet longer (48hr) depletion significantly altered the microglia response. This suggests that microglia rely on glycogen reserves for metabolic flexibility and to fuel their inflammatory responses.
Conclusion:
Microglia utilise their internal stores of glycogen to fuel their inflammatory responses to amyloid (in vivo) and to LPS (in vitro). Glycogen regulated microglia responses may represent a novel therapeutic strategy for targeting microglia inflammation in neurodegenerative diseases.
Insights
Microglia utilize internal glycogen stores to fuel inflammatory responses in Alzheimer's Disease (AD). Targeting glycogen metabolism may offer a novel therapeutic strategy for neurodegenerative diseases.
Area of Science:
- Neuroimmunology
- Metabolic pathways in neurodegeneration
- Alzheimer's Disease pathogenesis
Background:
- Chronic inflammatory microglia are central to Alzheimer's Disease (AD) pathology, exhibiting high metabolic demands.
- Sustained hyperglycemia is a known risk factor for AD, highlighting the critical role of glucose metabolism.
- Understanding microglia metabolic fueling is crucial for developing therapeutic strategies in neurodegenerative diseases.
Purpose of the Study:
- To investigate the metabolic pathways utilized by microglia during Alzheimer's Disease progression.
- To determine the role of glucose and glycogen in microglia inflammatory responses.
Main Methods:
- Microglia were isolated from APP-NL-G-F mice at 1, 3, and 6 months of disease progression.
- Proteomic analysis and mass spectrometry were employed to interrogate microglia.
- In vitro glucose depletion experiments were conducted to assess microglia inflammatory responses.
Main Results:
- Microglia significantly upregulated glycolysis and inflammatory protein expression at 6 months.
- Glucose receptor expression decreased, while glycogen breakdown proteins increased.
- Microglia relied on glycogen reserves for metabolic flexibility and inflammatory responses, with prolonged glucose depletion altering their function.
Conclusions:
- Microglia use internal glycogen stores to fuel inflammatory responses to amyloid and LPS.
- Glycogen-modulated microglia responses present a potential therapeutic target for neuroinflammation in neurodegenerative diseases.
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