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Animal Models to Study the Role of Kynurenine Pathway in Mood, Behavior, and Cognition

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Targeting the Broadly Pathogenic Kynurenine Pathway

Abstract

Mood disorders and cognitive dysfunctions are often associated with a number of serious conditions/diseases, including aging and obesity. These disorders not only impair the quality of life of affected subjects but emerge as potent risk factors for related health outcomes. Understanding their etiology represents therefore a major public health challenge. In the present chapter, we provide converging evidence showing that inflammatory processes, and more importantly related activation of the kynurenine pathway, are involved in the development of neuropsychiatric comorbidities. Specifically, we give an overview of how experimental studies performed in relevant animal models of immune activation that can be used to better understand the role of kynurenine pathway in mood, behavior, and cognition bring strong support to this notion. We report experimental data demonstrating the link between inflammation-induced brain activation of indoleamine 2,3-dioxygenase (IDO), the enzyme that metabolizes tryptophan along the kynurenine pathway, and mood and cognitive alterations. Beyond highlighting the role of IDO in that context, we also show how animal models can contribute to identify the mechanisms by which kynurenine pathway activation promotes behavioral alterations. Lastly, we briefly present recent experimental data pointing to a broadly role of this pathway in a medical condition associated with inflammation, namely obesity. Altogether, these findings may prove valuable for introducing new therapeutic strategies targeting the kynurenine pathway to treat behavioral alterations.

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Abbreviations

IL-1β:

Interleukin-1β

TNF-α:

Tumor necrosis factor-α

IFN:

Interferons

LPS:

Lipopolysaccharide

BCG:

Bacillus Calmette-Guerin

IDO:

Indoleamine 2,3-dioxygenase

3-HK:

3-Hydroxykynurenine

QUIN:

Quinolinic acid

KA:

Kynurenic acid

BDNF:

Brain-derived neurotrophic factor

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Authors and Affiliations

  1. Laboratory of “Nutrition and Integrative Neurobiology”, INRA, UMR 1286, University of Bordeaux, 33076, Bordeaux, France

    Nathalie Castanon

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  1. Nathalie Castanon
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Correspondence to Nathalie Castanon .

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  1. Chairman, Department of Neurosurgery, Wayne State University, Detroit, Michigan, USA

    Sandeep Mittal

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Castanon, N. (2015). Animal Models to Study the Role of Kynurenine Pathway in Mood, Behavior, and Cognition. In: Mittal, S. (eds) Targeting the Broadly Pathogenic Kynurenine Pathway. Springer, Cham. https://doi.org/10.1007/978-3-319-11870-3_25

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