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Neuroinflammation is a complex biological process related to a variety of pathologies, often requiring better understanding in order to develop new, targeted therapeutic interventions. Within this context, multimodal Mass Spectrometry Imaging (MSI) has been used to characterise molecular changes in neuroinflammation for biomarker discovery not possible to other techniques. In this study, molecules including bioactive lipids were detected across inflamed regions of the brain in rats treated with lipopolysaccharide (LPS). The detected lipids may be acting as inflammatory mediators of the immune response. We identified that N-acyl-phosphatidylethanolamine (NAPE) species accumulated in the inflamed area. The presence of these lipids could be related to the endocannabinoid (eCB) signalling system, mediating an anti-inflammatory response from microglial cells at the site of injury to balance pro-inflammation and support neuronal protection. In addition, polyunsaturated fatty acids (PUFAs), specifically n-3 and n-6 species, were observed to accumulate in the area where LPS was injected. PUFAs are directly linked to anti-inflammatory mediators resolving inflammation. Finally, acylcarnitine species accumulated around the inflammation region. Accumulation of these molecules could be due to a deficient β-oxidation cycle. [ABSTRACT FROM AUTHOR]

Glucocorticoids (GCs) are widely prescribed anti-inflammatory medicines, but their use can lead to metabolic side-effects. These may occur through direct actions of GCs on peripheral organs, but could also be mediated by the hypothalamic AgRP neurons, which can increase food intake and modify peripheral metabolism. Therefore, the aim of this study was to examine the metabolic effects of chronic treatment with the GC corticosterone (Cort, 75 μg/ml in drinking water) in mice lacking the glucocorticoid receptor (GR) on AgRP neurons. Female AgRP-GR KO mice had delayed onset of Cort-induced hyperphagia. However, AgRP-GR KO had little impact on the increased body weight or adiposity seen with 3 weeks Cort treatment. Cort caused hepatic steatosis in control mice, but in Cort treated female AgRP-GR KO mice there was a 25% reduction in liver lipid content and lower plasma triglycerides. Additionally, Cort treatment led to hyperinsulinaemia, but compared to controls, Cort-treated AgRP-GR KO mice had both lower fasting insulin levels and lower insulin levels during a glucose tolerance test. In conclusion, these data indicate that GCs do act through AgRP neurons to contribute, at least in part, to the adverse metabolic consequences of chronic GC treatment. [ABSTRACT FROM AUTHOR]