title: Glucocorticoid sensitization of microglia in a genetic mouse model of obesity and diabetes.
abstract: db/db mice are a model of obesity and diabetes due to their lack of functional leptin receptors, which leads to insulin resistance, elevated corticosterone levels, and persistent inflammation. Because stress-induced elevations in glucocorticoids sensitize microglia to immune challenges, we hypothesized that corticosteroids might act similarly in the diabetic brain. To test this hypothesis, db/db and wildtype mice were treated with the glucocorticoid synthesis inhibitor metyrapone every day for 2weeks. This treatment revealed corticosterone-dependent increases in microglial number and accumulation of the pro-inflammatory cytokines interleukin 1beta and tumor necrosis factor alpha in the hippocampus of db/db mice. Analysis of microglial responses to lipopolysaccharide stimulation revealed that glucocorticoids lower the threshold for release of pro-inflammatory cytokines, underscoring the role of corticosteroids as a precipitating factor for neuroinflammation in obesity and diabetes.
authors.affiliation: Department of Physiology, Georgia Regents University, Augusta, GA, 30912, USA.
authors.forename: Aditi
authors.initials: A
authors.lastname: Dey
authors.affiliation: Department of Physiology, Georgia Regents University, Augusta, GA, 30912, USA.
authors.forename: Shuai
authors.initials: S
authors.lastname: Hao
authors.affiliation: Department of Physiology, Georgia Regents University, Augusta, GA, 30912, USA.
authors.forename: Joanna R
authors.initials: JR
authors.lastname: Erion
authors.affiliation: Department of Physiology, Georgia Regents University, Augusta, GA, 30912, USA.
authors.forename: Marlena
authors.initials: M
authors.lastname: Wosiski-Kuhn
authors.affiliation: Department of Physiology, Georgia Regents University, Augusta, GA, 30912, USA.
authors.forename: Alexis M
authors.initials: AM
authors.lastname: Stranahan
mesh_terms: D000818:Animals; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000378:metabolism*; D004195:Disease Models, Animal; D005938:Glucocorticoids / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D008797:Metyrapone / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D009765:Obesity / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D005938:Glucocorticoids; D018836:Inflammation Mediators; D008797:Metyrapone
keywords: Corticosterone; Glucocorticoid; Hippocampus; Inflammation; Obesity