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| |  Eleonore Beurel, Ph.D. Assistant Professor, Department Psychiatry & Behavioral Sciences, Neuroscience Program Affiliated Faculty Member 305 243 0263 (office) 305-243-3955 (fax) 1011 NW 15th Street, Gautier room 415
B.S., University Pierre and Marie Curie, Paris, France, 2000
M.S., University Pierre and Marie Curie, Paris, France, 2001
Ph.D, University Pierre and Marie Curie, Paris, France, 2001-2005
Postdoctoral fellow, Department of Psychiatry, University of Alabama at Birmingham, 2005-2011 Assistant Professor, Department of Psychiatry, University of Miami, since 2011 |
| Accumulating evidence shows inflammation strongly influences the development and treatment of depression, a debilitating disease with a lifetime incidence of ~20%. Markers of Inflammation often are increased in the serum of depressed patients, interferon administration can induce depression, "psychological" stresses that can induce depression increase inflammatory cytokines, administration of inflammatory cytokines induces depression-like behaviors, in humans increased cytokines associated with a mild stimulation of the primary host defense system has negative effects on emotions, antidepressants have anti-inflammatory effects, and immune activation in patients with major depression is associated with resistance to antidepressant treatment. Therefore, in order to understand and design improved therapeutics for depression, it is important to identify mechanisms regulating neuroinflammation, inflammatory molecule accumulation in the CNS. Glycogen synthase kinase-3 (GSK3) recently was found to be a powerful regulator of cytokine production and GSK3 inhibitors promote tolerance to inflammation, down-regulating inflammatory responses to repeated inflammatory stimuli, which may be particularly important in controlling chronic inflammation that is likely associated with mood disorders. GSK3 also has profound influences in mood disorders, it is inhibited by mood stabilizers and antidepressants, pharmacological or genetic reduction of GSK3 activity reduces depression-like behaviors, and evidence in postmortem brain samples and serum from humans indicate GSK3 is abnormally active in mood disorders. We recently found GSK3 is activated during depression. Taken together, these findings suggest that the pro-inflammatory action of GSK3 may contribute to its promotion of mood disorders, and that the therapeutic actions of mood stabilizers and antidepressants that inhibit GSK3 may involve anti-inflammatory effects. Thus, studies of the inflammation system provide focus to study how GSK3 regulates key processes that are likely involved in mood disorders. These aims provide independent but associated goals that will identify new mechanisms by which dysregulated GSK3 can contribute to mood disorders and identify how therapeutic interventions ameliorate these outcomes. |
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Beurel E, Jope RS. Differential regulation of STAT family members by glycogen synthase kinase-3. Journal of Biological Chemistry 283: 21934-21944 (2008) PMC 2494932
Beurel E, Jope RS. Lipopolysaccharide-induced interleukin-6 production is controlled by glycogen synthase kinase-3 and STAT3 in the brain. Journal of Neuroinflammation 6: 9-20 (2009) PMC2660311
Polter A, Beurel E, Yang S, Garner R, Song L, Miller CA, Sweatt JD, McMahon L, Bartolucci AA, Li X, Jope RS. Deficiency in the inhibitory serine-phosphorylation of glycogen synthase kinase-3 increases sensitivity to mood disturbances. Neuropsychopharmacology 35: 1761-1774 (2010) PMC2891528
Beurel E, Jope RS. Glycogen synthase kinase-3 controls inflammatory tolerance in astrocytes. Neuroscience 169: 1063-1070 (2010) PMC2914115
Beurel E, Michalek SM, Jope RS. Innate and adaptive immune responses regulated by glycogen synthase kinase-3. Trends in Immunology 31: 24-31 (2010) PMC2818223
Beurel E, Song L, Jope RS. Inhibition of glycogen synthase kinase-3 is necessary for the rapid antidepressant effect of ketamine in mice. Molecular Psychiatry 16(11):1068-1070 (2011) PMC3200424
Beurel E, Yeh WI, Michalek SM, Harrington LE, Jope RS. Glycogen synthase kinase-3 is an early determinant in the differentiation of pathogenic Th17 cells. Journal of Immunology 186:1391-1398 (2011) PMC3125578 |
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