Brain, behavior, and immunity
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Brain Behav. Immun. · Aug 2014
CX3CL1-mediated macrophage activation contributed to paclitaxel-induced DRG neuronal apoptosis and painful peripheral neuropathy.
Painful peripheral neuropathy is a dose-limiting side effect of paclitaxel therapy, which hampers the optimal clinical management of chemotherapy in cancer patients. Currently the underlying mechanisms remain largely unknown. Here we showed that the clinically relevant dose of paclitaxel (3×8mg/kg, cumulative dose 24mg/kg) induced significant upregulation of the chemokine CX3CL1 in the A-fiber primary sensory neurons in vivo and in vitro and infiltration of macrophages into the dorsal root ganglion (DRG) in rats. ⋯ Furthermore, depletion of macrophage by systemic administration of clodronate inhibited paclitaxel-induced allodynia. Blocking CX3CL1 decreased activation of p38 MAPK in the macrophage, and inhibition of p38 MAPK activity blocked the neuronal apoptosis and development of mechanical allodynia induced by paclitaxel. These findings provide novel evidence that CX3CL1-recruited macrophage contributed to paclitaxel-induced DRG neuronal apoptosis and painful peripheral neuropathy.
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Brain Behav. Immun. · Aug 2014
Cytokine polymorphisms are associated with fatigue in adults living with HIV/AIDS.
Fatigue has been associated with inflammation and cytokine activity among adults, but this relationship has not been evaluated among adults living with HIV. Diurnal patterns of fatigue have been previously identified in adults with HIV/AIDS. Thus, the purpose of this study was to describe these fatigue patterns in relation to cytokine plasma concentrations and gene polymorphisms. ⋯ The IL1B and TNFA polymorphisms were not associated with plasma levels of IL-1β or TNFα, respectively. This study strengthens the evidence for an association between inflammation and fatigue. In this chronic illness population, the cytokine polymorphisms associated with high levels of morning and evening fatigue provide direction for future personalized medicine intervention research.
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Brain Behav. Immun. · Aug 2014
ReviewImmune system: a possible nexus between cannabinoids and psychosis.
Endocannabinoid system is involved in the regulation of the brain-immune axis. Cannabis consumption is related with the development, course, and severity of psychosis. The epidemiological evidence for increased occurrence of immunological alterations in patients with psychosis has not been sufficiently addressed. The aim of this review is to establish whether there is any scientific evidence of the influence of cannabinoids on aspects of immunity that affect susceptibility to psychotic disorder induction. ⋯ The actions of cannabinoids through the immune system are quite regular and predictable in the peripheral but remain fuzzy in the central nervous system. Despite this uncertainty, it may be hypothesized that exposure to exocannabinoids, in particular during adolescence might prompt immunological dysfunctions that potentially cause a latent vulnerability to psychosis. Further investigations are warranted to clarify the relationship between the immunological effects of cannabis and psychosis.
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Brain Behav. Immun. · Aug 2014
Reduced sleep, stress responsivity, and female sex contribute to persistent inflammation-induced mechanical hypersensitivity in rats.
Studies in humans suggest that female sex, reduced sleep opportunities and biological stress responsivity increase risk for developing persistent pain conditions. To investigate the relative contribution of these three factors to persistent pain, we employed the Sciatic Inflammatory Neuritis (SIN) model of repeated left sciatic perineurial exposures to zymosan, an inflammatory stimulus, to determine their impact upon the development of persistent mechanical hypersensitivity. Following an initial moderate insult, a very low zymosan dose was infused daily for eight days to model a sub-threshold inflammatory perturbation to which only susceptible animals would manifest or maintain mechanical hypersensitivity. ⋯ Hypothalamic-pituitary-adrenal (HPA) axis hyporesponsive Lewis rats exhibited the most robust development of mechanical hypersensitivity and HPA axis hyperresponsive Fischer 344 rats matched the Lewis rats' mechanical hypersensitivity throughout the latter four days of the protocol. If HPA axis phenotype does indeed influence these findings, the more balanced responsivity of Sprague Dawley rats would seem to promote resilience in this paradigm. Taken together, these findings are consistent with what is known regarding persistent pain development in humans.
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Brain Behav. Immun. · Aug 2014
Neuroinflammation in bipolar disorder - A [(11)C]-(R)-PK11195 positron emission tomography study.
The "monocyte-T-cell theory of mood disorders" regards neuroinflammation, i.e. marked activation of microglia, as a driving force in bipolar disorder. Microglia activation can be visualized in vivo using [(11)C]-(R)-PK11195 PET. Indirect evidence suggests the hippocampus as a potential focus of neuroinflammation in bipolar disorder. We aim to determine if there is increased [(11)C]-(R)-PK11195 binding to activated microglia in the hippocampus of patients with bipolar I disorder when compared to healthy controls. ⋯ This study is the first to demonstrate the presence of focal neuroinflammation in the right hippocampus in bipolar I disorder.