Changes in the NMR Metabolic Profile of Human Microglial Cells Exposed to Lipopolysaccharide or Morphine

Abstract

Microglial cells play a major role in host defense of the central nervous system. Once activated, several functional properties are up-regulated including migration, phagocytosis, and secretion of inflammatory mediators such as cytokines and chemokines. Little, if anything, is known about the metabolic changes that occur during the activation process. High-resolution 1H nuclear magnetic resonance spectra obtained from perchloric acid extracts of human microglial cell cultures exposed to lipopolysaccharide (LPS) or morphine were used to both identify and quantify the metabolites. We found that human microglia exposed to LPS had increased concentrations of glutamate and lactate, whereas the cells exposed to morphine had decreased concentrations in creatinine, taurine, and thymine. Glutamate and creatinine were the key metabolites differentiating between the two stimuli. These results are discussed in terms of activation and differences in the inflammatory response of human microglial cells to LPS and morphine.

Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy

“…We found increased LAC in ME/CFS patients in the bilateral insula, bilateral parietal cortex, left hippocampus, left middle cingulate gyrus, left precuneus, right thalamus, right rolandic operculum, left temporal cortex, right calcarine sulcus, right fusiform gyrus, right lingual gyrus, and cerebellum. LAC is a byproduct of anaerobic cell metabolism (glycolysis) that is not found at high levels in the healthy brain, but is produced by various immune cells under inflammatory conditions (Dienel, 2012;El Ghazi et al, 2010). Because anaerobic glycolysis results in much less efficient synthesis of adenosine triphosphate (ATP) than healthy metabolism, the resultant energy deficits at the cellular level may drive the profound fatigue experienced by ME/CFS patients (Castro-Marrero et al, 2013;Lawson, Hsieh, March, & Wang, 2016;Myhill, Booth, & McLaren-Howard, 2013).…”

Exploring the Neuroimmunopharmacology of Opioids: An Integrative Review of Mechanisms of Central Immune Signaling and Their Implications for Opioid Analgesia

“…Despite genetic knockout studies demonstrating the profound influence of Toll/IL-1 receptor signaling on opioid actions Hutchinson et al, 2010b,c;, such opioid-TLR responses are not always consistent (El Ghazi et al, 2010). Moreover, why has this TLR activity of opioids not been observed until now?…”

Magnetic Resonance Spectroscopy discriminates the response to microglial stimulation of wild type and Alzheimer’s disease models

“…Administration of lipopolysaccharide (LPS) is the most common procedure to activate microglia through stimulation of toll-like receptor 4, which dose-dependently induces secretion of inflammatory mediators causing neuroinflammation at moderate doses to severe sepsis at very high doses. When stimulating human microglial cells in culture with LPS, elevated glutamate and lactate levels were found 19 , while an increase in lactate levels and a decrease in choline were observed with ex vivo MRS after an acute extreme dose of LPS (32 mg/kg i.p. administration) 20 .…”