Chapter 25: Animal models to study the role of kynurenine pathway in mood, behavior, and cognition

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 infl ammatory processes, and more importantly related activation of the kynurenine pathway, are involved in the development of neuropsychiatric comorbidities. Specifi cally, 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 infl ammation-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 briefl y present recent experimental data pointing to a broadly role of this pathway in a medical condition associated with infl ammation, namely obesity. Altogether, these fi ndings may prove valuable for introducing new therapeutic strategies targeting the kynurenine pathway to treat behavioral alterations.