Brain, behavior, and immunity
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Brain Behav. Immun. · Jul 2014
Benefit of physical fitness against inflammation in obesity: role of beta adrenergic receptors.
Evidence shows that both poor physical fitness and obesity are linked to low-grade inflammation and inflammatory diseases. However, their relative roles on inflammation and underlying mechanisms remain unclear. Given the inhibitory effect of catecholamines on inflammatory cytokine production, we speculated that compromised responsiveness of immune cells' beta adrenergic receptors (β-ARs) to agonists may be associated with constitutively elevated levels of inflammatory cytokines. ⋯ Monocytic β-AR sensitivity was negatively associated with inflammatory marker levels and diminished in obese individuals; however, when fitness was controlled for, the significant weight group differences in β-AR sensitivity disappeared. Our findings indicate that better cardiorespiratory fitness protects against obesity-related low-grade inflammation and β-AR desensitization. Given the significance of β-AR function in pathogenesis of various diseases, clinical implications of its role in the fitness-inflammation association among the obese are profound.
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Brain Behav. Immun. · May 2014
Src family kinases involved in CXCL12-induced loss of acute morphine analgesia.
Functional interactions between the chemokine receptor CXCR4 and opioid receptors have been reported in the brain, leading to a decreased morphine analgesic activity. However the cellular mechanisms responsible for this loss of opioid analgesia are largely unknown. Here we examined whether Src family-kinases (SFK)-linked mechanisms induced by CXCR4 contributed to the loss of acute morphine analgesia and could represent a new physiological anti-opioid signaling pathway. ⋯ Similar effects were obtained after an intrathecal injection of a specific SFK inhibitor, PP2 (10μg). Furthermore, PP2 abrogated CXCL12-induced decrease in morphine analgesia by suppressing SFK activation in the spinal cord. In conclusion, our data highlight that CXCL12-induced loss of acute morphine analgesia is linked to Src family kinases activation.
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Brain Behav. Immun. · May 2014
Elevated C-reactive protein levels may be a predictor of persistent unfavourable symptoms in patients with mild traumatic brain injury: a preliminary study.
The pathogenesis of persistent unfavourable outcomes following mild traumatic brain injury (mTBI) are not fully understood. Low-grade systemic inflammation might contribute to the development of persistent unfavourable outcomes in patients with mTBI. We used plasma high-sensitivity C-reactive protein (CRP) levels as the biomarker of systemic inflammation to investigate whether elevated CRP levels were associated with persistent adverse outcomes in these patients. ⋯ However, elevated CRP levels were not associated with persistent physiological problems (OR, 1.330; 95% CI, 0.905-1.956; p=0.146). Furthermore, three adjusted models did not essentially affect the OR of elevated CRP levels for these persistent unfavourable outcomes. Among patients with mTBI, baseline elevated CRP levels may be an independent predictor of persistent persistent PCS, psychological problems and cognitive impairment.
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Brain Behav. Immun. · May 2014
Minocycline rescues decrease in neurogenesis, increase in microglia cytokines and deficits in sensorimotor gating in an animal model of schizophrenia.
Adult neurogenesis in the hippocampus is impaired in schizophrenic patients and in an animal model of schizophrenia. Amongst a plethora of regulators, the immune system has been shown repeatedly to strongly modulate neurogenesis under physiological and pathological conditions. It is well accepted, that schizophrenic patients have an aberrant peripheral immune status, which is also reflected in the animal model. ⋯ Treatment with the antibiotic minocycline (3mg/kg/day) normalized microglial cytokine production in the hippocampus and rescued neurogenesis and behavior. We could also show that enhanced microglial TNF-α and IL-1β production in the hippocampus was accompanied by a decrease in the pro-proliferative TNFR2 receptor expression on neuronal progenitor cells, which could be attenuated by minocycline. These findings strongly support the idea to use anti-inflammatory drugs to target microglia activation as an adjunctive therapy in schizophrenic patients.
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Brain Behav. Immun. · May 2014
Postoperative cognitive dysfunction: Involvement of neuroinflammation and neuronal functioning.
Postoperative cognitive dysfunction (POCD) has been hypothesized to be mediated by surgery-induced inflammatory processes, which may influence neuronal functioning either directly or through modulation of intraneuronal pathways, such as the brain derived neurotrophic factor (BDNF) mediated pathway. To study the time course of post-surgical (neuro)inflammation, changes in the BDNF-pathway and POCD, we subjected 3months old male Wistar rats to abdominal surgery and implanted a jugular vein catheter for timed blood sampling. Cognition, affective behavior and markers for (neuro)inflammation, BDNF and neurogenesis were assessed at 1, 2 and 3weeks following surgery. ⋯ The observed differences in time course following surgery and relation to plasma IL-6 suggest cognitive dysfunction and mood changes comprise distinct features of postoperative behavioral impairment. The postoperative changes in neuroinflammation, BDNF and neurogenesis may represent aspects of the underlying mechanism for POCD. Future research should be aimed to elucidate how these players interact.