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Kynurenines, Gender and Neuroinflammation; Showcase Schizophrenia

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Abstract

Schizophrenia has a clear sexual dimorphism in age of onset and progression. The underlying mechanisms of this dimorphism are not known, but may be found in the interactions of sex hormones with the tryptophan catabolising kynurenine pathway. Schizophrenia is associated with general inflammation and disruption of glutamatergic and dopaminergic signalling. Metabolites of the kynurenine pathway have been shown to be immunomodulatory and have effects on glutamatergic and dopaminergic signalling. This review discusses the currently available literature on sex hormones and their effect on the kynurenine pathway in the context of the glutamatergic, dopaminergic and immunological features of schizophrenia.

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Abbreviations

3HAA:

3-hydroxy anthranilic acid

3HAO:

3-hydroxyanthranilate

3HK:

3-hydroxy kynurenine

ACMS:

Aminocarboxymuconate semialdehyde

ACMSD:

Aminocarboxymuconate semialdehyde decarboxylase

IDO1:

Indoleamine 2,3-dioxygenase

IFN-γ:

Interferon gamma

KAT:

Kynurenine aminotransferase

KMO:

Kynurenine monooxygenase

KP:

Kynurenine Pathway

KYN:

Kynurenine

KYNA:

Kynurenic acid

NMDAR:

N-methyl-D-aspartate receptor

PIC:

Picolinic acid

QPRT:

Quinolinate phosphoribosyltransferase

QUIN:

Quinolinic acid

TDO:

Tryptophan-2,3-dioxygenase

TRP:

Tryptophan

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Acknowledgments

The authors would like to thank M. James Hutson for his assistance with Fig. 4. Ms Josien de Bie is supported by an international scholarship from Macquarie University. Prof Guillemin is supported by the National Health and Medical Research Council (NHMRC) and the Australian Research Council (ARC). Prof Guillemin is also a recipient of the Australian Research Council Future Fellowship Award (FT120100397). Dr Lim is a recipient of the Society of Mental Health Research (SMHR) Australia Early Career Fellowship.

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  1. Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, 2109, Australia

    J. de Bie, C. K. Lim & G. J. Guillemin

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de Bie, J., Lim, C.K. & Guillemin, G.J. Kynurenines, Gender and Neuroinflammation; Showcase Schizophrenia. Neurotox Res 30, 285–294 (2016). https://doi.org/10.1007/s12640-016-9641-5

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