Brain, behavior, and immunity
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Brain Behav. Immun. · Jul 2015
Effects of insomnia disorder and knee osteoarthritis on resting and pain-evoked inflammatory markers.
Osteoarthritis is the most prevalent arthritic condition. Systemic inflammatory cytokines appear to have an important role in the onset and maintenance of the disease. Sleep disturbances are prevalent in osteoarthritis and associated with alterations in systemic inflammatory cytokines, suggesting a common pathophysiology across these conditions. ⋯ These findings highlight the utility of laboratory pain testing methods for understanding individual differences in inflammatory cytokines. Moreover, our findings provide evidence for amplified pain-evoked pro-inflammatory cytokine reactivity among older adults with clinically diagnosed insomnia disorder, even after controlling for individual differences in BMI and age. Additional research will be required determine whether an amplified pain-related cytokine response contributes to OA, and possibly other age-related disease, associated with insomnia disorder.
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Brain Behav. Immun. · Jul 2015
Resolvins AT-D1 and E1 differentially impact functional outcome, post-traumatic sleep, and microglial activation following diffuse brain injury in the mouse.
Traumatic brain injury (TBI) is induced by mechanical forces which initiate a cascade of secondary injury processes, including inflammation. Therapies which resolve the inflammatory response may promote neural repair without exacerbating the primary injury. Specific derivatives of omega-3 fatty acids loosely grouped as specialized pro-resolving lipid mediators (SPMs) and termed resolvins promote the active resolution of inflammation. ⋯ RvE1 treated mice displayed a higher proportion of ramified microglia and lower proportion of activated rod microglia in the cortex compared to saline or AT-RvD1 treated brain-injured mice. Thus, RvE1 treatment modulated post-traumatic sleep and the inflammatory response to TBI, albeit independently of improvement in motor and cognitive outcome as seen in AT-RvD1-treated mice. This suggests AT-RvD1 may impart functional benefit through mechanisms other than resolution of inflammation alone.
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Brain Behav. Immun. · May 2015
Reduction of kynurenic acid to quinolinic acid ratio in both the depressed and remitted phases of major depressive disorder.
Low-grade inflammation is characteristic of a subgroup of currently depressed patients with major depressive disorder (dMDD). It may lead to the activation of the kynurenine-metabolic pathway and the increased synthesis of potentially neurotoxic metabolites such as 3-hydroxykynurenine (3HK) and quinolinic acid (QA), relative to kynurenic acid (KynA). Nevertheless, few studies have examined whether abnormalities in this pathway are present in remitted patients with MDD (rMDD). ⋯ Further, there was an inverse correlation between KynA/QA and anhedonia in the dMDD group, while in the rMDD group, there was a negative correlation between lifetime number of depressive episodes and KynA/QA as well as a positive correlation between the number of months in remission and KynA/QA. Our results raise the possibility that a persistent abnormality exists within the kynurenine metabolic pathway in MDD that conceivably may worsen with additional depressive episodes. The question of whether persistent abnormalities in kynurenine metabolism predispose to depression and/or relapse in remitted individuals remains unresolved.
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Brain Behav. Immun. · May 2015
Adenosine 2A receptor agonism: A single intrathecal administration attenuates motor paralysis in experimental autoimmune encephalopathy in rats.
A single intrathecal dose of adenosine 2A receptor (A2AR) agonist was previously reported to produce a multi-week reversal of allodynia in two different models of neuropathic pain in addition to downregulating glial activation markers in the spinal cord. We aimed to determine whether a single intrathecal administration of an A2AR agonist was able to attenuate motor symptoms induced by experimental autoimmune encephalopathy. ⋯ OX-42, a marker of microglial activation, was significantly attenuated in the lumbar spinal cord following A2AR administration compared to vehicle. Therefore, A2AR agonists attenuate motor symptoms of EAE by acting on A2AR in the spinal cord.
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Brain Behav. Immun. · May 2015
Peripheral indoleamine 2,3-dioxygenase 1 is required for comorbid depression-like behavior but does not contribute to neuropathic pain in mice.
Chronic pain frequently co-occurs with major depressive disorder but the mechanisms are poorly understood. We investigated the contribution of indoleamine 2,3-dioxygenase-1 (IDO1), a rate-limiting enzyme in the conversion of tryptophan to neurotoxic metabolites, to this comorbidity using the spared nerve injury (SNI) model of neuropathic pain in mice. SNI resulted in unilateral mechanical allodynia, reduced social interaction, and increased immobility in the forced swim test without changes in locomotor activity. ⋯ Mechanical allodynia was similar in WT and Ido1(-/-) mice. In conclusion, our findings show for the first time that neuropathic pain is associated with an increase of Ido1 in liver, but not brain, downstream of spinal cord IL-1β signaling and that Ido1 mediates comorbid depression. Moreover, comorbidity of neuropathic pain and depression are only partially mediated by a common mechanism because mechanical hyperalgesia develops independently of Ido1.