Gene expression changes in the hypothalamus provide evidence for regionally-selective changes in IL-1 and microglial markers after acute stress

Blandino, Peter; Barnum, Christopher J.; Solomon, Lyvia G.; Larish, Yaniv; Lankow, Benjamin S.; Deak, Terrence

doi:10.1016/j.bbi.2009.04.013

Cited by 119 publications

(123 citation statements)

References 57 publications

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“…The same stress that increased hippocampal cytokine and chemokine levels did not increase cytokines and chemokines in the prefrontal cortex. While there is no information regarding the cause of this differential inflammatory response to stress, previous studies have reported that inescapable foot or tail shocks do not increase IL-6 or IL-1 in the prefrontal cortex (Nguyen et al, 2000;Deak et al, 2003;Blandino et al, 2009). On the other hand, cytokines in the prefrontal cortex or cortex were reported to increase after acute social defeat stress (Audet et al, 2011), chronic restraint stress (Garate et al, 2013), and chronic mild stress (Garate et al, 2011;You et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

“…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).…”

Section: Introductionmentioning

confidence: 99%

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

Cheng

Jope

Beurel

2016

Psychoneuroendocrinology

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Cheng

Jope

Beurel

2016

Psychoneuroendocrinology

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“…Female rats in the stress group were exposed to 80 inescapable foot shocks (FS; 80 shocks, 1 mA for 5 s each, intertrial interval = 90 s) over the course of approximately 2 h, as previously described [21,23]. Briefly, the FS chamber measured 30.5 × 26.5 × 33 cm (L × W × H; Habitest Chamber, model H10-11R-TC-SF; Coulbourn Instruments, Allentown, Pa., USA).…”

Section: Methodsmentioning

confidence: 99%

“…In response to certain types of stress, microglia release multiple inflammatory mediators, including tumor necrosis factor (TNF)-α, prostaglandin E 2 , nitric oxide, and interleukin-1β (IL-1), among others [5,21]. The paraventricular nucleus (PVN) of the hypothalamus, a key regulatory nucleus of the hypothalamic-pituitary-adrenal (HPA) axis [22], is one of the main sites expressing inflammatory mediators following stress exposure [21,23,24]. IL-1 is a proinflammatory cytokine produced as an early step in the initiation of stress-induced neuroimmune responses [25,26], and seems to be responsible for several physiological and behavioral changes following stress exposure, including fever, anorexia, decreased exploratory and social activity, and an altered sensitivity to pain [27,28,29].…”

Section: Introductionmentioning

confidence: 99%

Effects of the Estrous Cycle and Ovarian Hormones on Central Expression of Interleukin-1 Evoked by Stress in Female Rats

Arakawa

Hueston

et al. 2014

Neuroendocrinology

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Exposure to stressors such as foot shock (FS) leads to increased expression of multiple inflammatory factors, including the proinflammatory cytokine interleukin-1 (IL-1) in the brain. Studies have indicated that there are sex differences in stress reactivity, suggesting that the fluctuations in gonadal steroid levels across the estrous cycle may play a regulatory role in the stress-induced cytokine expression. The present studies were designed to investigate the role of 17-β-estradiol (E₂) and progesterone (Pg) in regulating the cytokine response within the paraventricular nucleus (PVN) of the hypothalamus through analysis of gene expression with real-time RT-PCR. Regularly cycling female rats showed a stress-induced increase in PVN IL-1 levels during the diestrous, proestrous, and estrous stages. During the metestrous stage, no change in IL-1 levels was seen following FS; however, estrogen receptor (ER)-β levels did increase. Ovariectomy resulted in an increase in PVN IL-1 levels, which was attenuated by treatment with estradiol benzoate (10 or 50 µg), indicating an E₂-mediated anti-inflammatory effect. Ovariectomized rats treated with Pg (500 or 1,250 µg) showed no alteration in IL-1 levels, but Pg did up-regulate ER-β gene expression. The results from the current study implicate a potential mechanism through which high availability of endogenous Pg during the metestrous stage increases ER-β sensitivity, which in turn attenuates the PVN IL-1 response to stress. Thus, the interaction between gonadal steroid hormones and their central receptors may exert a powerful inhibitory effect on neuroimmune consequences of stress throughout the estrous cycle.

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“…This is considered to be an important adaptive action by glucocorticoids, with dissipation of the 'fight/flight' response heightening immune defences and vigilance beyond basal levels and promoting more vigorous reactions to persisting or impending threats (Sapolsky et al, 2000;Johnson et al, 2002;Sorrells et al, 2009). Specifically within the central nervous system (CNS), it has been demonstrated that short term stress can modulate microglial immunophenotype to sensitise a neuroinflammatory response which may be exaggerated in subsequent inflammatory challenges (Blandino et al, 2006;Frank et al, 2007;Sugama et al, 2007;Blandino et al, 2009;Sugama et al, 2009;Sugama et al, 2011). Activated microglia upregulate antigen presentation molecules such as major histocompatibility complex, increase phagocytic activity, generate pro-inflammatory cytokines and reactive oxygen/nitrogen species, overall inducing a neuroinflammatory response (de Pablos et al, 2006;Frank et al, 2007;Colton, 2009).…”

Section: Introductionmentioning

confidence: 99%

The effects of short term stress on the central and peripheral nitrergic system

Chen¹

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The mammalian stress response is generated by several integrated neural systems that allow rapid adaptation to homeostatic disturbances. This is principally mediated through the hypothalamicpituitary-adrenal axis which mobilises energy reserves by adrenal glucocorticoids. This in turn accelerates cellular metabolism which consequently increases free radical formation through the mitochondrial electron transport chain. Excess generation of free radicals such as reactive oxygen and nitrogen species (RNS) may potentially cause damage to fatty acids, proteins, and DNA by oxidative and nitrosative stress. Nitric oxide is a ubiquitous signalling molecule belonging to the family of RNS and is endogenously synthesised from ʟ-arginine by nitric oxide synthase (NOS).Three distinct subtypes of NOS have been identified, with the neuronal and endothelial isoforms being constitutively expressed enzymes responsible for synaptic signalling and smooth muscle relaxation. The inducible isoform is primarily present in cells of the inflammatory immune system where its activity is transcriptionally induced by cytokines and other inflammatory agents and thus, is thought to play an important role in immunomodulation. Recently, a number of studies have demonstrated that the nitrergic system have significant implications in neuropsychiatric disorders including anxiety and depression. Specifically, chronic stress-induced hippocampal neuronal NOS upregulation is responsible for glucocorticoid receptor downregulation, a factor linked to the development of depressive disorders. Although stress and nitrergic signalling are intrinsically linked in pathological states, little is known about the acute physiology between these two systems.Therefore, the primary aim of this thesis was to establish the profile of nitrosative changes in peripheral blood and brain regions known to be impacted by stress following an acute psychological challenge. The observed changes were subsequently investigated by employing a pharmacological intervention using a novel stress-alleviating and anti-inflammatory endocannabinoid enhancer. To achieve the aims for this thesis, Male Wistar rats aged 5-7 weeks postnatal were maintained under control conditions or subjected to acute stress. Blood samples were collected at time-points immediately before, during, and following treatment in order to estimate the levels of stress hormones and redox parameters including oxidative/nitrosative status, glutathione and glutathione disulphide ratio, and lipid peroxidation. Post mortem neural tissue was collected and specific brain regions were isolated for the determination of nitrosative status, NOS enzymatic activity, and relative gene expression of stress and nitrergic-related genes. Following the establishment of these measurements, a separate group of animals was used to examine the effects of endocannabinoid modulation on the nitrergic and inflammatory-related indicators following acute stress.ii We found that exposure to a single episode of psychological stress causes e...

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Gene expression changes in the hypothalamus provide evidence for regionally-selective changes in IL-1 and microglial markers after acute stress

Cited by 119 publications

References 57 publications

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

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

Effects of the Estrous Cycle and Ovarian Hormones on Central Expression of Interleukin-1 Evoked by Stress in Female Rats

The effects of short term stress on the central and peripheral nitrergic system

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