The impact of chronic stress on behaviour, inflammation and adult hippocampal neurogenesis

Abstract

Chronic stress can alter the immune system, adult hippocampal neurogenesis and induce anxiety-and depressive-like behaviour in rodents. However, no study to date has discriminated between the effect(s) of different types of stress on all these behavioural and biological outcomes. Moreover, while the unpredictable chronic mild stress (UCMS) model of depression remains one of the most commonly used stress models, it does not entirely follow the trajectory of clinical depression, which can take months after stress exposure to manifest. Therefore, this PhD thesis has two main goals; (1) to investigate the effect(s) of physical stress, modelled by repeated injection, and psychosocial stress, modelled by social isolation, on behaviour, immune system functioning, and neurogenesis in adult male mice, and (2) to develop and characterise a more chronic and translatable model of UCMS that measures changes in behaviour, inflammation and adult hippocampal neurogenesis six weeks after UCMS, and incorporates a period of social isolation to represent social withdrawal, which can accompany or precede the development of depression.

Several novel findings emanate from this thesis. First, my work highlights how the type of stress exposure does indeed matter, given that distinct types of chronic stress can differentially alter behavioural and biological responses in adult male mice. For instance, physical stress promotes an anxiety-like phenotype, decreases systemic inflammation, and decreases neurogenesis. In contrast, psychosocial stress promotes a depressive-like phenotype, increases systemic inflammation, and increases the number of mature neuroblasts in the dentate gyrus. Second, this thesis puts forward an alternative, yet appropriately robust UCMS model of depression, one that successfully induces depressive-like behaviour, alters astrocyte biology, and reduces neurogenesis.

The work presented in the thesis contributes to our understanding of the impact of chronic stress on immune system functioning and adult hippocampal neurogenesis, and its association with depressive-like behaviour.

Date of Award	2018
Original language	English
Awarding Institution	King's College London
Supervisor	Carmine Pariante (Supervisor), Cathy Fernandes (Supervisor) & Sandrine Thuret (Supervisor)