Microglia serve as a neuroimmune substrate for stress-induced potentiation of CNS pro-inflammatory cytokine responses

Frank, Marion E.; Baratta, Michael V.; Sprunger, David; Watkins, Linda R.; Maier, Steven F.

doi:10.1016/j.bbi.2006.03.005

Cited by 512 publications

(432 citation statements)

References 45 publications

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“…Microglia in brain respond to both stress and alcohol with increases in innate immune signaling molecules such as cytokines. Stress sensitizes brain to endotoxin responses (Frank et al., 2007), and stress hormones appear to enhance brain innate immune stress responses (Frank et al., 2016; Sorrells et al., 2009). Interestingly, this is consistent with studies finding innate immune signaling contributes to the development of AUD (Crews et al., 2017; de Timary et al., 2017).…”

Section: Discussionmentioning

confidence: 99%

Alcohol and Stress Activation of Microglia and Neurons: Brain Regional Effects

Walter

Vetreno

Crews

2017

Alcoholism Clin & Exp Res

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BackgroundCycles of alcohol and stress are hypothesized to contribute to alcohol use disorders. How this occurs is poorly understood, although both alcohol and stress activate the neuroimmune system—the immune molecules and cells that interact with the nervous system. The effects of alcohol and stress on the neuroimmune system are mediated in part by peripheral signaling molecules. Alcohol and stress both enhance immunomodulatory molecules such as corticosterone and endotoxin to impact neuroimmune cells, such as microglia, and may subsequently impact neurons. In this study, we therefore examined the effects of acute and chronic ethanol (EtOH) on the corticosterone, endotoxin, and microglial and neuronal response to acute stress.MethodsMale Wistar rats were treated intragastrically with acute EtOH and acutely stressed with restraint/water immersion. Another group of rats was treated intragastrically with chronic intermittent EtOH and acutely stressed following prolonged abstinence. Plasma corticosterone and endotoxin were measured, and immunohistochemical stains for the microglial marker CD11b and neuronal activation marker c‐Fos were performed.ResultsAcute EtOH and acute stress interacted to increase plasma endotoxin and microglial CD11b, but not plasma corticosterone or neuronal c‐Fos. Chronic EtOH caused a lasting sensitization of stress‐induced plasma endotoxin, but not plasma corticosterone. Chronic EtOH also caused a lasting sensitization of stress‐induced microglial CD11b, but not neuronal c‐Fos.ConclusionsThese results find acute EtOH combined with acute stress enhanced plasma endotoxin, as well as microglial CD11b in many brain regions. Chronic EtOH followed by acute stress also increased plasma endotoxin and microglial CD11b, suggesting a lasting sensitization to acute stress. Overall, these data suggest alcohol and stress interact to increase plasma endotoxin, resulting in enhanced microglial activation that could contribute to disease progression.

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Section: Discussionmentioning

confidence: 99%

Alcohol and Stress Activation of Microglia and Neurons: Brain Regional Effects

Walter

Vetreno

Crews

2017

Alcoholism Clin & Exp Res

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“…If animals are exposed to an acute stressor 24 hours prior to LPS treatment, the result is an enhanced inflammatory response across several measures, including plasma and brain levels of IL-1β and TNF-α (Johnson et al 2002a). More specifically, prior acute stress was found to enhance LPS-induced production of IL-1β in microglia (Frank et al 2006). The enhanced response in the brain is relatively long-lived, being observable for at least four days following the stressor (Johnson et al 2002b).…”

Section: Gcs Prior To Versus During or After Inflammationmentioning

confidence: 99%

An inflammatory review of glucocorticoid actions in the CNS

Sorrells¹,

Sapolsky²

2007

Brain, Behavior, and Immunity

397

283

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In recent years the classic view that glucocorticoids, the adrenal steroids secreted during stress, are universally anti-inflammatory has been challenged at a variety of levels. It was first observed that under some circumstances, acute GC exposure could have pro-inflammatory effects on the peripheral immune response. More recently, chronic exposure to GCs has been found to have pro-inflammatory effects on the specialized immune response to injury in the central nervous system. Here we review the evidence that in some cases, glucocorticoids can increase pro-inflammatory cell migration, cytokine production, and even transcription factor activity in the brain. We consider how these unexpected effects of glucocorticoids can co-exist with their well-established anti-inflammatory properties, as well as the considerable clinical implications of these findings.

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“…These studies have especially focused on activation of microglia (Tsuda et al, 2003(Tsuda et al, , 2005Inoue et al, 2004;Allen and Barres, 2005;Frank et al, 2007;Zhang et al, 2007), but there is growing evidence that astroglia may also be important (Watkins et al, 1997(Watkins et al, , 2001Sweitzer et al, 1999;Raghavendra et al, 2004;Tanga et al, 2004;Haydon and Carmignoto, 2006;Qin et al, 2006;Lan et al, 2007). Central sensitization is considered a crucial process underlying the development of chronic pain states (Dubner and Basbaum, 1994;Sessle, 2000;Woolf and Salter, 2006), and we have recently demonstrated that intrathecal application of fluoroacetate (FA), a specific inhibitor of the metabolic enzyme aconitase, which is a component of the tricarboxylic acid cycle in astroglia (Fonnum et al, 1997;Schousboe and Waagepetersen, 2006), attenuates central sensitization in functionally identified nociceptive neurons of trigeminal subnucleus caudalis without affecting normal nociceptive processing (Xie et al, 2007).…”

Section: Introductionmentioning

confidence: 99%