A comparison of mindfulness-based stress reduction and an active control in modulation of neurogenic inflammation.

Psychological stress is a major provocative factor of symptoms in chronic inflammatory conditions. In recent years, interest in addressing stress responsivity through meditation training in health-related domains has increased astoundingly, despite a paucity of evidence that reported benefits are specific to meditation practice. We designed the present study to rigorously compare an 8-week Mindfulness-Based Stress Reduction (MBSR) intervention to a well-matched active control intervention, the Health Enhancement Program (HEP) in ability to reduce psychological stress and experimentally-induced inflammation. The Trier Social Stress Test (TSST) was used to induce psychological stress and inflammation was produced using topical application of capsaicin cream to forearm skin. Immune and endocrine measures of inflammation and stress were collected both before and after MBSR training. Results show those randomized to MBSR and HEP training had comparable post-training stress-evoked cortisol responses, as well as equivalent reductions in self-reported psychological distress and physical symptoms. However, MBSR training resulted in a significantly smaller post-stress inflammatory response compared to HEP, despite equivalent levels of stress hormones. These results suggest behavioral interventions designed to reduce emotional reactivity may be of therapeutic benefit in chronic inflammatory conditions. Moreover, mindfulness practice, in particular, may be more efficacious in symptom relief than the well-being promoting activities cultivated in the HEP program.

Accuracy of hippocampal network activity is disrupted by neuroinflammation: rescue by memantine.

Understanding how the hippocampus processes episodic memory information during neuropathological conditions is important for treatment and prevention applications. Previous data have shown that during chronic neuroinflammation the expression of the plasticity related behaviourally-induced immediate early gene Arc is altered within the CA3 and the dentate gyrus; both of these hippocampal regions show a pronounced increase in activated microglia. Low doses of memantine, a low to moderate affinity open channel uncompetitive N-Methyl-d-aspartate receptor antagonist, reduce neuroinflammation, return Arc expression to control levels and attenuate cognitive deficits induced by lipopolysaccharide. Here we investigate whether neuroinflammation affects the accuracy of information processing in the CA3 and CA1 hippocampal regions and if this is modified by memantine treatment. Using the immediate early gene-based brain-imaging method called cellular analysis of temporal activity by fluorescence in situ hybridization, it is possible to detect primary transcripts at the genomic alleles; this provides exceptional temporal and cellular resolution and facilitates the mapping of neuronal activity. Here, we use this method to compare the neuronal populations activated by two separate experiences in CA1 and CA3 and evaluate the accuracy of information processing during chronic neuroinflammation. Our results show that the CA3 pyramidal neuron activity is not stable between two exposures to the same environment context or two different contexts. CA1 networks, however, do not differ from control conditions. These data suggest that during chronic neuroinflammation, the CA3 networks show a disrupted ability to encode spatial information, and that CA1 neurons can work independently of CA3. Importantly, memantine treatment is able to partially normalize information processing in the hippocampus, suggesting that when given early during the development of the pathology memantine confers neuronal and cognitive protection while indirectly prevents pathological microglial activation.

Neuroinflammation and cognitive function in aged mice following minor surgery.

Following surgery, elderly patients often suffer from postoperative cognitive dysfunction (POCD) which can persist long after physical recovery. It is known that surgery-induced tissue damage activates the peripheral innate immune system resulting in the release of inflammatory mediators. Compared to adults, aged animals demonstrate increased neuroinflammation and microglial priming that leads to an exaggerated proinflammatory cytokine response following activation of the peripheral immune system. Therefore, we sought to determine if the immune response to surgical trauma results in increased neuroinflammation and cognitive impairment in aged mice. Adult and aged mice underwent minor abdominal surgery and 24h later hippocampal cytokines were measured and working memory was assessed in a reversal learning version of the Morris water maze. While adult mice showed no signs of neuroinflammation following surgery, aged mice had significantly increased levels of IL-1beta mRNA in the hippocampus. Minor surgery did not result in severe cognitive impairment although aged mice that underwent surgery did tend to perseverate in the old target during reversal testing suggesting reduced cognitive flexibility. Overall these results suggest that minor surgery leads to an exaggerated neuroinflammatory response in aged mice but does not result in significantly impaired performance in the Morris water maze.

Differences of peripheral inflammatory markers between mild cognitive impairment and Alzheimer's disease.

Multiple pathogenic factors may contribute to the pathophysiology of Alzheimer's disease (AD). Peripheral markers have been used to assess biochemical alterations associated with AD and mild cognitive impairment (MCI) involved in its pathophysiology. The present study was conducted to evaluate inflammatory peripheral markers in elderly patients with MCI, patients with AD and normal elderly subjects. We measured plasma levels of different cytokines (IL-6, TNF-alpha and IFN-alpha) and platelet levels of cyclooxigenase-2 (COX-2) from 34 patients with MCI, 45 patients with AD and 28 age-matched control subjects. MCI and AD patients showed similarities in TNF-alpha and COX-2 levels, and differences in IL-6 and INF-alpha. Whereas augmented IL-6 levels have been found in AD patients, a significant increase in INF-alpha has been detected only in patients with MCI possibly associated with the depression stage frequently found in cognitive impairment. In conclusion, inflammatory response may be an early factor in AD development and these changes in circulating markers are possibly related to the progression of MCI to AD.