TY - JOUR
T1 - Glucocorticoid sensitization of microglia in a genetic mouse model of obesity and diabetes
AU - Dey, Aditi
AU - Hao, Shuai
AU - Erion, Joanna R.
AU - Wosiski-Kuhn, Marlena
AU - Stranahan, Alexis M.
N1 - Funding Information:
We are grateful to Dr. Matthew Frank for initial training on the microglia isolation technique, and to Dr. Steven Maier for generously allowing a lab visit for this purpose. This work was funded in part by the National Institutes of Health Grant K01DK100616 to A.M.S., and by summer fellowships from the Diabetes and Obesity Discovery Institute of Georgia Regents University to A.D. and S.H.
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
KW - Corticosterone
KW - Glucocorticoid
KW - Hippocampus
KW - Inflammation
KW - Obesity
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U2 - 10.1016/j.jneuroim.2014.01.013
DO - 10.1016/j.jneuroim.2014.01.013
M3 - Article
C2 - 24534266
AN - SCOPUS:84896395852
SN - 0165-5728
VL - 269
SP - 20
EP - 27
JO - Journal of Neuroimmunology
JF - Journal of Neuroimmunology
IS - 1-2
ER -
