Do changes in microglial status underlie neurogenesis impairments and depressive-like behaviours induced by psychological stress? A systematic review in animal models

Abstract

Stress may have a negative effect on mental health and is the primary environmental risk factor in the aetiology of depression. Nevertheless, the neurobiological mechanisms underlying this mood disorder remain poorly characterized. The hippocampus is a target structure of the adverse effects of stress, and hippocampal neurogenesis plays a crucial role. However, we do not know the mechanisms by which stress impacts neurogenesis. Recent studies indicate that changes in neuroinflammation, primarily via microglial cells, may play an essential role in this process. However, the relationship between stress, microglial changes, and alterations in neurogenesis and their involvement in the development of depression is poorly characterized. For this reason, this systematic review aims to synthesise and evaluate current studies that have investigated the relationship between these variables. Taken together, the revised data, although not entirely conclusive, seem to suggest that microglial changes induced by psychological stress regulate neurogenesis and in turn may be responsible for the development of depressive-like behaviours, but other factors that influence these stressful experiences should not be dismissed.

Keywords: Animal models; Depression; Microglia; Neurogenesis; Neuroinflammation; Psychosocial stress; Systematic review.

Fig. 1

Flow diagram for literature selection, following the PRISMA guidelines, for the development of the present systematic review.

Fig. 2

I) Representation of the different stress procedures used in the 17 articles selected in this systematic review, and classified in early-life (A) or adult (B) stress. II) Different behavioural tests to measure the effect of psychosocial stress on depression-like behaviour. The tests are shown classified by the categories of: behavioural tests for loss of motivation, lack of energy and anhedonia assessing (A); coping strategies tests (B); social interaction test (C); anxiety-like behavioural tests (D); cognitive domains (E) and motor symptoms (F). Note that the last one category (motor symptoms) also uses EPM, OFT, Barnes Test and MWM. Also comment that, mice have been represented in behavioural tests as if they had depressive-like behaviours. Abbreviations. CUMS: Chronic Unpredictable Mild Stress; CWIRS: Chronic Water Immersion Restraint Stress; EPM: Elevated Plus Maze; FST: Forced Swimming Test; MWM: Morris Water Maze; OFT: Open Field Test; ORT: Object Recognition Test; RSDS: Repeated Social Defeat Stress; SD: Sleep Deprivation; SPT: Sucrose Preference Test; TST: Tail Suspension Test.

Fig. 3

Schematic representation of the cascade of inflammatory events induced by psychosocial stress and involved in the development of depression. The most relevant markers of inflammation and neurogenesis used in the reviewed studies are indicated. In addition, neurogenic processes and the inflammatory response pathway are specified. Additionally, we also include SIRT1, an important member of the sirtuin family, induces deacetylation of the NF-kB subunit p65, thereby inhibiting its activity. Continuous arrows represent a direct relation, and discontinuous arrows and indirect relation.