Microglial Function during Glucose Deprivation: Inflammatory and Neuropsychiatric Implications
Open accessAbstract
Inflammation is increasingly recognized as a contributor to the pathophysiology of neuropsychiatric disorders, including depression, anxiety disorders and autism, though the factors leading to contextually inappropriate or sustained inflammation in pathological conditions are yet to be elucidated. Microglia, as the key mediators of inflammation in the CNS, serve as likely candidates in initiating pathological inflammation and as an ideal point of therapeutic intervention. Glucose deprivation, as a component of the pathophysiology of ischemia or occurring transiently in diabetes, may serve to modify microglial function contributing to inflammatory injury. To this end, primary microglia were cultured from postnatal rat brain and subject to glucose deprivation in vitro. Microglia were characterized for their proliferation, phagocytic function and secretion of inflammatory factors, and tested for their capacity to respond to a potent inflammatory stimulus. In the absence of glucose, microglia remained capable of proliferation, phagocytosis and inflammatory activation and showed increased release of inflammatory factors after presentation of an inflammatory stimulus. Glucose-deprived microglia demonstrated increased phagocytic activity and decreased accumulation of lipids in lipid droplets over a 48-h timecourse, suggesting they may use scavenged lipids as a key alternate energy source during metabolic stress. In the present manuscript, we present novel findings that glucose deprivation may sensitize microglial release of inflammatory mediators and prime microglial functions for both survival and inflammatory roles, which may contribute to psychiatric comorbidities of ischemia, diabetes and/or metabolic disorder.
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Certain metabolic states such as glucose starvation in microglia lead to lipid redistribution rather than de novo fatty acid synthesis.
“Additionally, certain metabolic states such as glucose starvation in microglia lead to lipid redistribution rather than de novo FA synthesis [74].”
From Lipoprotein Lipase Regulates Microglial Lipid Droplet Accumulation (2021) · cites this paper as [74]
The Results and Discussion propose lipid redistribution rather than de novo fatty acid synthesis as a possible explanation for lipid-droplet increases after LPS stimulation, including in glucose-deprived microglia. They do not establish that glucose deprivation itself causes redistribution, and the explanation is explicitly tentative. (LLM, conf=0.86)
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- Authors
- Churchward, M. A., Tchir, D. R., & Todd, K. G.
- Affiliations
- University of Alberta (CA)
- Corresponding author
- Todd, Kathryn G.
- Venue
- Molecular Neurobiology
- Published
- 2017-02-07
- Volume
- 55
- Issue
- 2
- Pages
- 1477-1487
- ISSN
- 0893-7648 (ISSN-L)
- 1559-1182
- PMC
- PMC5820372
- OpenAlex
- W2586839353
- Cited by
- 63
- References
- 121
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 11 · 2023: 11 · 2022: 6 · 2021: 10 · 2020: 7 · 2019: 6 · 2018: 2
- FWCI
- 2.04
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Molecular Neurobiology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Alberta Health Services
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- microglia, glucose deprivation, neuroinflammation, phagocytosis, microglial proliferation, inflammatory mediators, lipid droplets, metabolic stress, ischemia, diabetes mellitus, neuropsychiatric disorders, depression, anxiety disorders, autism spectrum disorder
- MeSH terms
- Animals, Brain, Cells, Cultured, Hypoglycemia, Inflammation, Phagocytosis, Microglia, Cell Proliferation, Rats
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