Endogenous glucocorticoids protect against TNF-alpha-induced increases in anxiety-like behavior in virally infected mice

Silverman, Milton; MacDougall, Matthew; Hu, Fang; Pace, Thaddeus W.W.; Miller, Andrew H.

doi:10.1038/sj.mp.4001921

Cited by 64 publications

(31 citation statements)

References 64 publications

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“…For example, transgenic mouse lines deficient in central signaling involving pro-inflammtaory cytokines, such as interleukin-1β (IL-1β) or tumor necrosis factor-α (TNF-α), consistently exhibit altered anxiety behavior in the elevated plus maze or open field test. (Silverman, Macdougall et al 2007;Koo and Duman 2009). Further, an infusion of IL-1β into the lateral ventricle is sufficient to induce anxiety like behavior in the elevated plus maze (Koo and Duman 2009).…”

Section: Introductionmentioning

confidence: 98%

The Role of Brain Interleukin-1 in Stress-Enhanced Fear Learning

Jones

Lebonville

Barrus

et al. 2014

Neuropsychopharmacol

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Posttraumatic stress disorder (PTSD) has been shown to be associated with pro-inflammatory markers, including elevated plasma levels of interleukin-1β (IL-1β). However, the precise role of neuroinflammation and central immune signaling on the development of this debilitating psychological disorder is not known. Here, we used stress-enhanced fear learning (SEFL), an animal model of the disorder, to examine the role of central IL-1β in PTSD. The results show that the severe stressor in SEFL induces a time-dependent increase in IL-1β immunoreactivity and mRNA expression within the dentate gyrus of the dorsal hippocampus (DH). There was no increase in IL-1β in the basolateral amygdala or the perirhinal cortex. Moreover, blocking the action of IL-1β following the severe stressor with IL-1 receptor antagonist (10 μg, intracerebroventricular (i.c.v.), 24 and 48 h after the stressor) prevented the development of SEFL. To provide further support for the role of IL-1β in the development of SEFL, we show that systemic morphine, a treatment which is known to reduce both PTSD and SEFL, also reduces IL-1β expression in the DH induced by the severe stressor. These studies provide the first evidence that IL-1 is involved SEFL and suggest that IL-1 signaling in the brain may have a critical role in the development of PTSD.

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Section: Introductionmentioning

confidence: 98%

The Role of Brain Interleukin-1 in Stress-Enhanced Fear Learning

Jones

Lebonville

Barrus

et al. 2014

Neuropsychopharmacol

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“…Benzodiazepines that bind to the GABA A receptor have been widely used clinically to treat anxiety, and mice deficient in GAD65 show increased anxiety-like behavior (Aihara et al ., 1994). Several cytokines and chemokines, including interferon α, C-C motif ligand 2 (CCL2, or MCP-1), and tumor necrosis factor α (TNF), are known to increase anxiety behavior ( Fahey et al ., 2007; Silverman et al ., 2007; Breese et al ., 2008). IL2 also appears to be an inducer of anxiety.…”

Section: Introductionmentioning

confidence: 99%

Essential role of interleukin-15 receptor in normal anxiety behavior

Hsuchou

et al. 2010

Brain, Behavior, and Immunity

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The interactions between the cytokine interleukin (IL)-15 and the classical neurotransmitter GABA have been shown in IL15Rα receptor knockout mice by observations of memory deficits and reduction of GABA. To test the hypothesis that IL15 affects anxiety-like behavior, knockout mice without IL15, IL15Rα, or the co-receptor IL2Rγ were subjected to open-field and elevated plus maze tests. All three strains showed reduction of anxiety, with greater changes in the IL15Rα knockout mice than in the IL15 or IL2Rγ knockout mice. This unexpected observation is opposite to the reported increase of anxiety in mice lacking other proinflammatory cytokines or their receptors. The reduced anxiety was not associated with changes in associated serum cytokines. However, western blotting, qPCR, and immunohistochemistry all showed that IL15Rα knockout mice had mild microgliosis and astrogliosis in the hippocampus. To determine whether this gliosis plays a role in decreasing anxiety, IL15Rα knockout mice were treated with minocycline, but this did not cause a change in open field performance. To determine whether IL15 plays a direct role in anxiety, wildtype mice were treated with IL15 by intraperitoneal injection. This also failed to cause a change in open field behavior under the experimental conditions tested. Thus, IL15Rα is essential for normal anxietylike behavior, but inhibition of gliosis in the fearless IL15Rα knockout mice or IL15 treatment of normal mice did not acutely modulate behavioral performance as tested.

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“…These cells release a range of chemokines and cytokines which allow for bidirectional communication between the brain and immune system. There is now very good evidence to suggest that cytokines directly modulate HPA axis activity (Dunn, 2000;Jara et al, 2006;Mastorakos and Ilias, 2006;Mulla and Buckingham, 1999;Rivest, 2001;Savastano et al, 1994;Torpy and Chrousos, 1996;Turnbull and Rivier, 1999), anxiety-and depression-related behaviour (Anisman and Merali, 1999;Breese et al, 2008;Connor and Leonard, 1998;Craddock and Thomas, 2006;Leonard, 2001;Leonard, 2006;Nautiyal et al, 2008;O'Brien et al, 2004;Schiepers et al, 2005;Silverman et al, 2007;Wichers and Maes, 2002) and pain (McMahon et al, 2005;Moalem and Tracey, 2006;Sommer and Kress, 2004;Thacker et al, 2007;Watkins et al, 2003;Wieseler-Frank et al, 2005a;Wieseler-Frank et al, 2005b). Our recent work (Roche et al, 2006;Roche et al, 2008), and that of others (Croci et al, 2003;Panikashvili et al, 2001;Smith et al, 2000;Smith et al, 2001a;Smith et al, 2001b), has demonstrated a role for the endocannabinoid system in regulating peripheral and brain cytokine responses to immune challenge/stress in vivo.…”

Section: Stress-induced Analgesiamentioning

confidence: 99%

Endocannabinoid-mediated modulation of stress responses: Physiological and pathophysiological significance

Finn¹

2010

Immunobiology

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The stress response is associated with a broad spectrum of physiological and behavioural effects including hypothalamo-pituitary-adrenal (HPA) axis activation, altered central nervous system activity, neuroimmune alterations, anxiety-and depressive-like behaviour and analgesia. While the acute stress response has essential survival value, chronic stress and dysfunction of the stress response can be maladaptive, contributing to the development and severity of psychiatric and pain disorders. The endogenous cannabinoid (endocannabinoid) system has emerged as an important lipid signalling system playing a key role in mediating and/or modulating behavioural, neurochemical, neuroendocrine, neuroimmune and molecular responses to stress. The weight of evidence, reviewed here, points largely to a system which serves to constrain HPA axis activity, facilitate adaptation or habituation of HPA axis and behavioural responses to stress, reduce anxiety-and depressive-like behaviour and mediate analgesic responses to unconditioned or conditioned stress. Possible involvement of the immune system and associated signalling molecules (e.g. cytokines) in endocannabinoid-mediated modulation of neuroendocrine and behavioural responses to stress is considered. The goal now should be to exploit our understanding of the role of the endocannabinoid system in fundamental stress physiology and pathophysiological processes to better understand and treat a range of stress-related disorders including anxiety, depression and pain.

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Endogenous glucocorticoids protect against TNF-alpha-induced increases in anxiety-like behavior in virally infected mice

Cited by 64 publications

References 64 publications

The Role of Brain Interleukin-1 in Stress-Enhanced Fear Learning

The Role of Brain Interleukin-1 in Stress-Enhanced Fear Learning

Essential role of interleukin-15 receptor in normal anxiety behavior

Endocannabinoid-mediated modulation of stress responses: Physiological and pathophysiological significance

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