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Rodent Models of Stress-Induced Depression: The Link Between Stress and Immune System Related Changes

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Book cover Immunology and Psychiatry

Part of the book series: Current Topics in Neurotoxicity ((Current Topics Neurotoxicity,volume 8))

Abstract

Bi-directional communication between the brain and immune system is a research area gaining in prominence in the search for biological factors associated with the development of a number of psychiatric disorders. In this regard, animal models make substantial contributions to our understanding of these interactions. For instance, long-term adaptive changes to the immune system, in response to stress, have been documented and include stress-induced desensitisation of immune cell glucocorticoid receptors (GR) and β2-adrenoceptors (AR) which in turn can impact on the ability of these factors to elicit their natural anti-inflammatory actions. It is of interest that psychological stress has been reported to induce microglial activation and pro-inflammatory cytokine expression in the central nervous system (CNS) in animal studies, and whilst there is little evidence of microglial activation or an increase in CNS cytokines in depressed humans to date, animal studies are providing important insights into the potential role of central inflammatory events in the pathophysiology of stress related psychiatric disorders. Stress can be linked to the development of a pro-inflammatory state, and it is of interest to consider the reciprocal impact of peripheral inflammatory mediators on the brain. In this regard, there is accumulating evidence that inflammation plays a role in the pathogenesis of major depressive illness. To further explore the behavioural effects associated with immune system activation, a number of animal models are currently in use and include a range of agents used to initiate immune activation including bacterial endotoxin lipopolysaccharide (LPS), the inflammatory cytokine interferon (IFN) alpha, inoculation with Bacille Calmette–Guerin (BCG), experimental autoimmune encephalitis (EAE) and administration of synthetic double stranded ribonucleic acid (dsRNA) polyinosinic:polycytidylic acid (poly-IC), a viral mimetic. Immune activation in these models provokes signs of depression which may be ameliorated following treatment with antidepressant drugs. Despite these findings the question as to how an immunological basis for a disorder can be reconciled with more traditional hypotheses including impairment of monoamine transmission and the functional impairment of neurotrophins remains to be addressed. In this regard, the activation of indoleamine 2,3 dioxygenase (IDO) and activation of the kynurenine pathway or the ability of cytokines to influence monoamine transport, receptor activation or neurotrophic factor expression are possibilities. The impact of inflammation on such systems is providing new avenues to develop a better understanding of the role of stress and related immune changes in the pathophysiology of depression and to find new and improved therapies to address current unmet clinical needs.

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  1. Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin 2, Ireland

    Barry McGuinness & Andrew Harkin

  2. The School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin 2, Ireland

    Andrew Harkin

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  1. University Clinic, Campus Innenstadt Psychiatry and Psychotherapy, Ludwig-Maximilians-University Munich, Munich, Germany

    Norbert Müller

  2. University Clinic, Campus Innenstadt PsychoNeuroImmunology Research Group, Ludwig-Maximilians-University Munich, Munich, Germany

    Aye-Mu Myint

  3. Institute fuer Laboratoriumsmedizin, Klinikum der Universitaet Muenchen, Muenchen, Germany

    Markus J. Schwarz

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McGuinness, B., Harkin, A. (2015). Rodent Models of Stress-Induced Depression: The Link Between Stress and Immune System Related Changes. In: Müller, N., Myint, AM., Schwarz, M. (eds) Immunology and Psychiatry. Current Topics in Neurotoxicity, vol 8. Springer, Cham. https://doi.org/10.1007/978-3-319-13602-8_3

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