Low-Level Stress Induces Production of Neuroprotective Factors in Wild-Type but Not BDNF+/- Mice: Interleukin-10 and Kynurenic Acid |
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Authors: | Allison M Dugan Jennifer M Parrott Laney Redus Julie G Hensler Jason C O’Connor |
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Institution: | Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, TX (Ms Dugan, Ms Parrott, Ms Redus, Dr Hensler, and Dr O’Connor); Audie L Murphy VA Hospital, South Texas Veterans Health System, San Antonio, TX (Dr O’Connor). |
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Abstract: | Background:Brain-derived neurotrophic factor (BDNF) deficiency confers vulnerability to stress, but the mechanisms are unclear. BDNF+/- mice exhibit behavioral, physiological, and neurochemical changes following low-level stress that are hallmarks of major depression. After immune challenge, neuroinflammation-induced changes in tryptophan metabolism along the kynurenine pathway mediate depressive-like behaviors.Methods:We hypothesized that BDNF+/- mice would be more susceptible to stress-induced neuroinflammation and kynurenine metabolism, so BDNF+/- or wild-type littermate mice were subject to repeated unpredictable mild stress. Proinflammatory cytokine expression and kynurenine metabolites were measured.Results:Unpredictable mild stress did not induce neuroinflammation. However, only wild-type mice produced the neuroprotective factors interleukin-10 and kynurenic acid in response to repeated unpredictable mild stress. In BDNF+/- mice, kynurenine was metabolized preferentially to the neurotoxic intermediate 3-hydroxykynurenine following repeated unpredictable mild stress.Conclusions:Our data suggest that BDNF may modulate kynurenine pathway metabolism during stress and provide a novel molecular mechanism of vulnerability and resilience to the development of stress-precipitated psychiatric disorders. |
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Keywords: | Kynurenine neuroinflammation vulnerability |
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