Objective: Targeting of microglial metabolism may be a potential therapeutic option for diseases such as PD [Parkinson’s Disease] and LBD [Lewy Body Dementia]. To establish the metabolic profile of neurotoxic and neuroprotective microglial cells [SIM-A9] using mass spectrometry. This investigation will further our understanding of how metabolic changes in immune cells affect the immune response.

Background: Microglia are resident innate immune cells of the brain, with multi-faceted functions including synapse pruning, removing dead cells and initiating immune responses. Microglia are immunosuppressive during homeostasis and have a classic branched morphology, while upon activation these cells become phagocytic, and have an amoeboid morphology. However, these states are highly plastic and interchangeable. Microglia have been implicated in several neurodegenerative diseases, and particularly in PD, they are thought to be consistently in an activated state, and thus contribute to neuroinflammation. However, very little is known about microglial bioenergetics.

Method: Microglial cells were plated into 4-well chamber slides to allow for the formation of a monolayer of cells. Prior to analysis, the culture media was removed and the wells were briefly washed. A liquid microjunction surface sampling probe was used to directly extract analytes from the surface of adherent cells by performing continuous spot sampling in three different regions of each well for 1 minute.  Extracts were run on a Thermo Scientific Q-Exactive mass spectrometer for and exact mass values were compared to the Human Metabolome Database to identify intracellular metabolites and lipids.

Results: Several lipids were identified from the phospholipid region of the spectrum, which corresponded to several different lipid classes, including ceramides d18:1_16:0 and d18:1_18:0. Ceramides are of specific interest as they have been implicated in PD and are linked to cognition and dementia.

Conclusion: Immunology is a fast growing area of potential therapeutic value in neurodegenerative diseases. Microglia can be crucial players for the treatment of diseases such as PD and LBD, and targeting their metabolism in order to change phenotype is central to this objective. It is therefore important to understand microglial metabolism in order to optimize immunotherapies for neurodegenerative diseases.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/a-study-of-microglial-metabolism-in-neuroinflammation/