Brain, behavior, and immunity
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Brain Behav. Immun. · Mar 2012
Mu opioid receptor activation modulates Toll like receptor 4 in murine macrophages.
Opioids have been shown to affect both innate and adaptive immunity. We previously showed that morphine affects the macrophage production of pro-inflammatory cytokines after LPS in a NFkB dependent manner. Toll like receptors (TLRs) play a crucial role in the signaling pathways which lead to NFkB activation. ⋯ Experiments with MOR KO mice and with DAMGO (MOR specific agonist) confirm that the effect of morphine on TLR4 mRNA in peritoneal macrophages is due to the MOR activation. Moreover the effect on TLR4 is blocked by PTX thus indicating the involvement of a G(i) protein after MOR binding. This work unveils a clear link between MOR activation and TLR4, suggesting a new possible mechanism at the basis of the peripheral immunosuppressive effect of opioids.
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Brain Behav. Immun. · Feb 2012
Randomized Controlled TrialSingle-trial conditioning in a human taste-endotoxin paradigm induces conditioned odor aversion but not cytokine responses.
Immunological responses to bacterial endotoxin can be behaviorally conditioned in rodents. However, it is unclear whether an acute systemic inflammatory response can be behaviorally conditioned in humans. Thus, in a double-blind placebo-controlled study, 20 healthy, male subjects received either a single injection of lipopolysaccharide (LPS) or saline together with a novel tasting beverage (conditioned stimulus, CS). ⋯ Sole presentation of the CS during evocation did induce neither alterations in body temperature nor changes in plasma cytokine levels. However, subjects in the experimental group rated the smell of the CS significantly more aversive compared to the control group. Employing endotoxin as a US in a single trial taste-immune conditioning paradigm in humans shows a behaviorally conditioned smell aversion but no learned alterations in cytokine levels.
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Brain Behav. Immun. · Feb 2012
ReviewNeuroimmunological effects of physical exercise in depression.
The search for an extended understanding of the causes of depression, and for the development of additional effective treatments is highly significant. Clinical and pre-clinical studies suggest stress is a key mediator in the pathophysiology of depression. Exercise is a readily available therapeutic option, effective as a first-line treatment in mild to moderate depression. ⋯ When clinical and pre-clinical data is taken together, exercise may reduce inflammation and oxidation stress via a multitude of cellular and humoral neuroimmune changes. Astrocytes, microglia and T cells have an antiinflammatory and neuroprotective functions via a variety of mechanisms. It is unknown whether exercise has effects on specific neuroimmune markers implicated in the pathogenesis of depression such as markers of immunosenescence, B or T cell reactivity, astrocyte populations, self-specific CD4+ T cells, T helper 17 cells or T regulatory cells.
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Brain Behav. Immun. · Jan 2012
Peripheral bacterial endotoxin administration triggers both memory consolidation and reconsolidation deficits in mice.
Peripherally administered inflammatory stimuli, such as lipopolysaccharide (LPS), induce the synthesis and release of proinflammatory cytokines and chemokines in the periphery and the central nervous system, and trigger a variety of neurobiological responses. Indeed, prior reports indicate that peripheral LPS administration in rats disrupts contextual fear memory consolidation processes, potentially due to elevated cytokine expression. We used a similar, but partially olfaction-based, contextual fear conditioning paradigm to examine the effects of LPS on memory consolidation and reconsolidation in mice. ⋯ Additionally, as hypothesized, LPS administered immediately following the fear memory trace reactivation session impaired memory reconsolidation processes. Four hours post-injection, both central cytokine and peripheral cytokine and chemokine levels were heightened in LPS-treated animals, with a simultaneous decrease in BDNF, but not Zif-268, mRNA. Collectively, these data reinforce prior work showing LPS- and cytokine-related effects on memory consolidation, and extend this work to memory reconsolidation.
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Brain Behav. Immun. · Nov 2011
TNFα is involved in neuropathic pain induced by nucleoside reverse transcriptase inhibitor in rats.
In patients with HIV/AIDS, neuropathic pain is a common neurological complication. Infection with the HIV itself may lead to neuropathic pain, and painful symptoms are enhanced when patients are treated with nucleoside reverse transcriptase inhibitors (NRTIs). The mechanisms by which NRTIs contribute to the development of neuropathic pain are not known. ⋯ Knockdown of TNFα with siRNA blocked the mechanical allodynia induced by ddC. Intrathecal administration of glial inhibitor or recombinant TNF soluble receptor, reversed mechanical allodynia induced by ddC. These results suggest that TNFα is involved in NRTI-induced neuropathic pain.