Stress-induced increases in hypothalamic IL-1: a systematic analysis of multiple stressor paradigms

Stress-induced neuroinflammation is mediated by GSK3-dependent TLR4 signaling that promotes susceptibility to depression-like behavior

“…These variable increases emphasize the limited understanding of mechanisms that differentially regulate the responses of hippocampal cytokines and chemokines to stress, and suggest that those displaying the largest increases may have the greatest impact on behavioral responses to stress. The lack of increase of hippocampal IL-1β after a single session of inescapable foot shocks is in agreement with previous studies showing that hippocampal IL-1β levels were not increased at several times after stress (Nguyen et al, 2000;O'Connor et al, 2003;Deak et al, 2003;Deak et al, 2005;Blandino et al, 2006;Blandino et al, 2009). The same stress that increased hippocampal cytokine and chemokine levels did not increase cytokines and chemokines in the prefrontal cortex.…”

“…Rodents exhibiting depression-like behaviors also have elevated brain cytokine levels (Goshen et al, 2008;Kreisel et al, 2014), and administration of inflammatory cytokines causes depressionlike behaviors in rodents (Bluthé et al, 2000;De la Garza et al, 2005;Dantzer and Kelley 2007;Palin et al, 2008;Fu et al, 2010). Acute inescapable tail shocks, acute or chronic restraint stress, and social defeat stress, all of which induce depressive-like behaviors in rodents, activate the inflammatory transcription factor nuclear factor-κB (NF-κB) and increase levels of the cytokines IL-1β, TNFα, IL-6 and IL-10 in rodent brains (Nguyen et al, 2000;Madrigal et al, 2002;O'Connor et al, 2003;Deak et al, 2003;Deak et al, 2005;Blandino et al, 2006;Blandino et al, 2009;Audet et al, 2011;Wohleb et al, 2011;You et al, 2011). In addition to inducing neuroinflammation, stress amplified the increases of inflammatory cytokines (e.g., IL-1β, TNFα) in rodent brains induced by peripheral administration of the inflammatory Toll-like receptor 4 (TLR4) agonist lipopolysaccharide (LPS) (Quan et al, 2001;Johnson et al, 2002;Johnson et al, 2003;Johnson et al, 2004;Munhoz et al, 2006;De Pablos et al, 2006;Frank et al, 2007;Espinosa-Oliva et al, 2009;Wohleb et al, 2012).…”

Chronic Nicotine Self-Administration Augments Hypothalamic–Pituitary–Adrenal Responses to Mild Acute Stress

“…Although the specificity for foot shock is an unexpected dimension of the cross-sensitization induced by nicotine SA, it is consistent with an emerging viewpoint on the HPA axis that emphasizes its discriminative rather than ubiquitous responsiveness to diverse stressors (Deak et al, 2005;Li et al, 1996). Such specificity might depend on neuronal plasticity induced by nicotine within brain areas that are preferentially involved in mediating the stress response to psychological stressors.…”

IL-1β is an essential mediator of the antineurogenic and anhedonic effects of stress

“…Rats were administered IL-1Ra or vehicle and then exposed to either foot-shock or immobilization (Fig. 1J), stressors that have been shown to increase central IL-1␤ (19). Foot-shock significantly decreased BrdU ϩ cell number in the DG (Fig.…”

“…One possibility is that excessive proinflammatory cytokines, particularly IL-1␤, contribute to the actions of stress. Animal studies demonstrate that exposure to stress increases IL-1␤ in several brain areas, including the hippocampus (17)(18)(19)(20), and central administration of IL-1␤ produces several stress-like effects, including activation of the hypothalamic-pituitary-adrenal (HPA) axis (17,21), inhibition of hippocampal long-term potentiation (22), down-regulation of hippocampal brain-derived neurotrophic factor (23), and impaired hippocampal-dependent contextual fear conditioning (24). In contrast, blockade of the receptor, IL-1RI that mediates the actions of IL-1␤ (25) inhibits these stress-like effects (23,24) and blocks the antiproliferative effects of INF-␣ in the hippocampus (26).…”