Table 1 Effects of individual nutrients on microglial phagocytosis
From: Metabolic regulation of microglial phagocytosis: Implications for Alzheimer's disease therapeutics
Nutrient | Manipulation | Effect on phagocytosis | Phagocytosed particle | Proposed mechanism | Microglial model | References |
|---|---|---|---|---|---|---|
Glucose | Glucose starvation (use of glucose-free medium) | ↑ | Fluorescent beads | Decrease in oxidative phosphorylation | Primary rat microglia | [40] |
Oxygen–glucose deprivation | ↑ | Fluorescent latex beads and myelin debris | Activation of RhoA/ROCK signalling; increased expression of complement receptor 3, CD11b, SR-A and ATP | Primary rat microglia | [43] | |
Treatment with deoxyglucose | ↑ | Carboxylate-modified latex microspheres | Depletion of ATP production | Primary rat microglia and BV2 microglia | [41] | |
Treatment with an inhibitor specific for GLUT1 (STF31) | ↓ | pHrodo Green S. aureus BioParticles | Decrease LPS + IFNγ-induced expression of TNFα, IL-1β, IL-6, and CCL2, iNOS; reduced IL-4-induced expression of Arg1 | B6M7 microglia and primary mouse microglia | [35] | |
Genetic ablation of hexokinase 2 | ↑ | Carboxyfluorescein-labelled Aβ42 | Upregulation of LPL expression, increase in lipid metabolism | Primary mouse microglia | [16] | |
Microparticles (sulfate microspheres) | Impaired mitochondrial function | Primary mouse microglia | [42] | |||
Lipids | α-linolenic acid supplementation | ↑ | Tau monomers and aggregates | Repolarization of axis of microtubule organizing center to facilitate microglial migration | N9 microglia | |
Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) supplementation | ↑ | Cy-3-labelled myelin | Reduced expression of TNFα and nitric oxide; increased expression of CD206 and/or TGF-β | Primary mouse microglia | [54] | |
Aβ42 | Decreased expression of CD40 and CD86 | CHME3 microglia | [57] | |||
Ketone bodies | β-hydroxybutyrate treatment | ↑ | Nile Red FluoSphere with 1-mm diameter microspheres | Activation of Akt-small RhoGTPase | BV2 microglia | [14] |
Pyruvate | Ethyl pyruvate treatment | ↑ | CFSE-conjugated myelin debris | Upregulation of Sox2 | BV2 and primary mouse microglia | [79] |
Lactate | Lactate supplementation | ↑ | FITIC-Dextran | Increase of CD68 expression | Primary rat microglia | [78] |
↓ | Fluorescent latex beads and pHrodo Red-labelled Aβ42 | HCAR1 activation | HMC3, N9 and primary mouse microglia | [80] |