Brain, behavior, and immunity
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Brain Behav. Immun. · Oct 2014
Neuropathic pain-induced depressive-like behavior and hippocampal neurogenesis and plasticity are dependent on TNFR1 signaling.
Patients suffering from neuropathic pain have a higher incidence of mood disorders such as depression. Increased expression of tumor necrosis factor (TNF) has been reported in neuropathic pain and depressive-like conditions and most of the pro-inflammatory effects of TNF are mediated by the TNF receptor 1 (TNFR1). Here we sought to investigate: (1) the occurrence of depressive-like behavior in chronic neuropathic pain and the associated forms of hippocampal plasticity, and (2) the involvement of TNFR1-mediated TNF signaling as a possible regulator of such events. ⋯ The onset of depressive-like behavior also coincided with increased hippocampal levels of TNF, and decreased expression of TNF receptor 2 (TNFR2), which were all fully restored after mice spontaneously recovered from pain. Notably, TNFR1(-/-) mice did not develop depressive-like symptoms after injury, nor were there changes in hippocampal neurogenesis and plasticity. Our data show that neuropathic pain induces a cluster of depressive-like symptoms and profound hippocampal plasticity that are dependent on TNF signaling through TNFR1.
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Brain Behav. Immun. · Oct 2014
Microglial NLRP3 inflammasome activation mediates IL-1β-related inflammation in prefrontal cortex of depressive rats.
Depression is an inflammatory disorder. Pro-inflammatory cytokine interleukin-1 beta (IL-1β) may play a pivotal role in the central nervous system (CNS) inflammation of depression. Here, we investigated IL-1β alteration in serum, cerebrospinal fluid (CSF) and prefrontal cortex (PFC) of chronic unpredictable mild stress (CUMS)-exposed rats, a well-documented model of depression, and further explored the molecular mechanism by which CUMS procedure induced IL-1β-related CNS inflammation. ⋯ The increased co-location of NLRP3 and ionized calcium binding adaptor molecule 1 (Iba1) protein expression supported that microglia in glial cells was the primary contributor for CUMS-induced PFC NLRP3 inflammasome activation in rats. These alterations in CUMS rats were restored by chronic treatment of the antidepressant fluoxetine, indicating that fluoxetine-mediated rat PFC IL-1β reduction involves both transcriptional and post-transcriptional regulatory mechanisms. These findings provide in vivo evidence that microglial NLRP3 inflammasome activation is a mediator of IL-1β-related CNS inflammation during chronic stress, and suggest a new therapeutic target for the prevention and treatment of depression.
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Brain Behav. Immun. · Oct 2014
Diet-induced obesity progressively alters cognition, anxiety-like behavior and lipopolysaccharide-induced depressive-like behavior: focus on brain indoleamine 2,3-dioxygenase activation.
Obesity is associated with a high prevalence of mood symptoms and cognitive dysfunctions that emerges as significant risk factors for important health complications such as cardiovascular diseases and type 2 diabetes. It is therefore important to identify the dynamic of development and the pathophysiological mechanisms underlying these neuropsychiatric symptoms. Obesity is also associated with peripheral low-grade inflammation and increased susceptibility to immune-mediated diseases. ⋯ However, 20 weeks of WD altered LPS-induced depressive-like behavior compared to LPS-treated lean mice and exacerbated hippocampal and hypothalamic proinflammatory cytokine expression and brain IDO activation. Taken together, these results show that WD exposure alters cognition and anxiety in unstimulated conditions and enhances activation of neurobiological mechanisms underlying depression after immune stimulation. They suggest therefore that obesity, and possibly obesity-associated inflammatory priming, may represent a vulnerability state to immune-mediated depressive symptoms.
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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.