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

Fig. 3.1

Animal models play an integral role in the development of an understanding of the effect of immune activation and inflammation on behavioural traits. Investigation of mechanisms linking immune–brain communication can be approached in a more invasive way in animal studies to elucidate changes in the brain in response to immune challenge. Such mechanisms include changes to the sensitivity of glucocorticoid/catecholamine receptors and regulation of the hypothalamic pituitary adrenal (HPA) or sympathoadrenal medullary (SAM) axes. Furthermore animals may be selectively bred or genetically engineered to help assist in evaluating a role for immune related mechanisms underlying depression and anxiety-related behaviours with associated neurobiological changes including the expression of neurotrophic factors or neurotransmitters such as serotonin or tryptophan metabolites related to kynurenine. Investigations of the CNS in humans are limited to CSF and post mortem tissue although MR and PET neuroimaging are providing investigators with a window into the brain and parallels may be drawn between outcomes in animal and human investigations. The possibility to translate from animal to human experiments in this way will pave the way for the development of biomarkers related to a role for the immune system in the pathophysiology of mood and anxiety disorders and future development of therapeutics which may target the immune system or brain microglial cells directly for a desirable clinical outcome. Abbreviations: ACTH adrenocorticotropic hormone, Adr adrenaline, CRH corticotropin releasing hormone, CSF cerebrospinal fluid, Hyp hypothalamus, IDO indoleamine 2,3 dioxygenase, NA noradrenaline, Pit pituitary, SAM sympathoadrenal medullary axis, TDO tryptophan 2,3 dioxygenase

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