title: Low-Level Stress Induces Production of Neuroprotective Factors in Wild-Type but Not BDNF+/- Mice: Interleukin-10 and Kynurenic Acid.
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.
authors.affiliation: 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).
authors.forename: Allison M
authors.initials: AM
authors.lastname: Dugan
authors.affiliation: 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).
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Parrott
authors.affiliation: 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).
authors.forename: Laney
authors.initials: L
authors.lastname: Redus
authors.affiliation: 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).
authors.forename: Julie G
authors.initials: JG
authors.lastname: Hensler
authors.affiliation: 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). oconnorj@uthscsa.edu.
authors.forename: Jason C
authors.initials: JC
authors.lastname: O'Connor
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D016753:Interleukin-10 / Q000378:metabolism*; D007736:Kynurenic Acid / Q000378:metabolism*; D007737:Kynurenine / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015213:Neuroimmunomodulation / Q000502:physiology; D013315:Stress, Psychological / Q000276:immunology*; D035501:Uncertainty
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C556062:IL10 protein, mouse; D016753:Interleukin-10; D007737:Kynurenine; D007736:Kynurenic Acid
keywords: Kynurenine; neuroinflammation; vulnerability