Low-Level Stress Induces Production of Neuroprotective Factors in Wild-Type but Not BDNF+/- Mice: Interleukin-10 and Kynurenic Acid.

Autor:	Dugan AM; 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)., Parrott JM; 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)., Redus L; 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)., Hensler JG; 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)., O'Connor JC; 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.
Jazyk:	angličtina
Zdroj:	The international journal of neuropsychopharmacology [Int J Neuropsychopharmacol] 2015 Aug 01; Vol. 19 (3), pp. pyv089. Date of Electronic Publication: 2015 Aug 01.
DOI:	10.1093/ijnp/pyv089
Abstrakt:	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. (© The Author 2015. Published by Oxford University Press on behalf of CINP.)
Databáze:	MEDLINE
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