Early-life stress and inflammation: A systematic review of a key experimental approach in rodents

Abstract

Repeated maternal separation is the most widely used pre-clinical approach to investigate the relationship between early-life chronic stress and its neuropsychiatric and physical consequences. In this systematic review, we identified 46 studies that conducted repeated maternal separation or single-episode maternal separation and reported measurements of interleukin-1b, interleukin-6, interleukin-10, tumour necrosis factor-alpha, or microglia activation and density. We report that in the short-term and in the context of later-life stress, repeated maternal separation has pro-inflammatory immune consequences in diverse tissues. Repeated maternal separation animals exhibit greater microglial activation and elevated pro-inflammatory cytokine signalling in key brain regions implicated in human psychiatric disorders. Notably, repeated maternal separation generally has no long-term effect on cytokine expression in any tissue in the absence of later-life stress. These observations suggest that the elevated inflammatory signalling that has been reported in humans with a history of early-life stress may be the joint consequence of ongoing stressor exposure together with potentiated neural and/or immune responsiveness to stressors. Finally, our findings provide detailed guidance for future studies interrogating the causal roles of early-life stress and inflammation in disorders such as major depression.

Does Low Grade Systemic Inflammation Have a Role in Chronic Pain?

“…Since then, increasing evidence has also revealed that depression and anxiety are tightly associated with low grade SCI ( Maes et al, 1995 ; Dowlati et al, 2010 ; Berk et al, 2013 ; Mazza et al, 2020 ; Poletti et al, 2021 ). Although recent studies reported that depression could be predisposed by childhood SCI ( Dutcher et al, 2020 ; Cao et al, 2021 ), it is still equivocal whether SCI is depressogenic and anxieogenic. Intriguingly, antidepressants, especially selective serotonin reuptake inhibitors ( Tynan et al, 2012 ; Gałecki et al, 2018 ; Hou et al, 2019 ; Wang et al, 2019 ; Dionisie et al, 2021 ) and TCA ( Xia et al, 1996 ; Maes et al, 1999 ; Kenis and Maes, 2002 ; Baumeister et al, 2016 ; Faissner et al, 2017 ), have powerful anti-inflammatory properties by decreasing the production/release of proinflammatory mediators and simultaneously increasing that of anti-inflammatory cytokines.…”

Effects of early‐life stress and sex on blood–brain barrier permeability and integrity in juvenile and adult rats

“…Thus, our MS procedure did not induce visible signs of inflammatory response in either juvenile or adult rats. The majority of data from the literature show that repeated MS does not affect the serum concentrations of proinflammatory cytokines, especially in basal conditions (for review, see Dutcher et al., 2020). This may result from a relative immaturity of the immune system during the MS procedure (Bogaert et al., 2009; Ortega et al., 2011).…”

NLRP3 Inflammasome Is Involved in Cocaine-Mediated Potentiation on Behavioral Changes in CX3CR1-Deficient Mice

“…Previous epidemiological studies have revealed that ELS, including brain trauma, mental and physical abuse, family violence, child maltreatment, etc., could increase the likelihood of drug addiction in later life [ 49 , 50 ]. Increased levels of peripheral and neural inflammation in ELS-experienced individuals were implied to play critical roles in the development of neuropsychiatric and/or neurodegenerative diseases [ 51 ]. Numerous rodent models showed that ELS was capable of having a long-term effect on microglial functional status.…”