Glucocorticoid sensitization of microglia in a genetic mouse model of obesity and diabetes

Aditi Dey, Shuai Hao, Joanna Ruth Appel, Marlena Wosiski-Kuhn, Alexis Michelle Stranahan

Research output: Contribution to journalArticle

32 Citations (Scopus)

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 2. weeks. 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.

Original languageEnglish (US)
Pages (from-to)20-27
Number of pages8
JournalJournal of Neuroimmunology
Volume269
Issue number1-2
DOIs
StatePublished - Jan 1 2014

Fingerprint

Genetic Models
Microglia
Glucocorticoids
Obesity
Corticosterone
Adrenal Cortex Hormones
Cytokines
Metyrapone
Leptin Receptors
Precipitating Factors
Interleukin-1beta
Lipopolysaccharides
Insulin Resistance
Hippocampus
Tumor Necrosis Factor-alpha
Inflammation
Brain

Keywords

  • Corticosterone
  • Glucocorticoid
  • Hippocampus
  • Inflammation
  • Obesity

ASJC Scopus subject areas

  • Immunology
  • Clinical Neurology
  • Immunology and Allergy
  • Neurology

Cite this

Glucocorticoid sensitization of microglia in a genetic mouse model of obesity and diabetes. / Dey, Aditi; Hao, Shuai; Appel, Joanna Ruth; Wosiski-Kuhn, Marlena; Stranahan, Alexis Michelle.

In: Journal of Neuroimmunology, Vol. 269, No. 1-2, 01.01.2014, p. 20-27.

Research output: Contribution to journalArticle

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