Low-level stress induces production of neuroprotective factors in wild-type but not BDNF+/- mice: Interleukin-10 and kynurenic acid

Allison M. Dugan, Jennifer M. Parrott, Laney Redus, Julie G. Hensler, Jason C. O'Connor

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1-5
Number of pages5
JournalInternational Journal of Neuropsychopharmacology
Volume19
Issue number3
DOIs
StatePublished - Jun 23 2015

Keywords

  • Kynurenine
  • neuroinflammation
  • vulnerability

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

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