Spatial Memory and Microglia Activation in a Mouse Model of Chronic Neuroinflammation and the Anti-inflammatory Effects of Apigenin.

Chronic neuroinflammation characterized by microglia reactivity is one of the main underlying processes in the initiation and progression of neurodegenerative diseases such as Alzheimer's disease. This project characterized spatial memory during healthy aging and prolonged neuroinflammation in the chronic neuroinflammatory model, glial fibrillary acidic protein-interleukin 6 (GFAP-IL6). We investigated whether chronic treatment with the natural flavonoid, apigenin, could reduce microglia activation in the hippocampus and improve spatial memory. GFAP-IL6 transgenic and wild-type-like mice were fed with apigenin-enriched or control chow from 4 months of age and tested for spatial memory function at 6 and 22 months using the Barnes maze. Brain tissue was collected at 22 months to assess microgliosis and morphology using immunohistochemistry, stereology, and 3D single cell reconstruction. GFAP-IL6 mice showed age-dependent loss of spatial memory recall compared with wild-type-like mice. Chronic apigenin treatment decreased the number of Iba-1+ microglia in the hippocampus of GFAP-IL6 mice and changed microglial morphology. Apigenin did not reverse spatial memory recall impairment in GFAP-IL6 mice at 22 months of age. GFAP-IL6 mice may represent a suitable model for age-related neurodegenerative disease. Chronic apigenin supplementation significantly reduced microglia activation, but this did not correspond with spatial memory improvement in the Barnes Maze.

Investigation Into the Effects of Tenilsetam on Markers of Neuroinflammation in GFAP-IL6 Mice.

PURPOSE: To test the short- and long-term effects of Tenilsetam on chronic neuroinflammation in the GFAP-IL6 mouse. METHODS: From 3 months of age, GFAP-IL6 mice were divided into 2 groups and fed with Tenilsetam enriched food pellets or control food pellets, respectively, for either 5 or 15 months. Total numbers of Iba-1+ microglia, TSPO+ cells were determined using an unbiased stereological method. Levels of methylglyoxal and TNF-α in the cerebellar homogenate were tested using HPLC and ELISA, respectively. RESULTS: Tenilsetam decreased the total number of Iba-1+ microglia in both the cerebellum and the hippocampus of GFAP-IL6 mice at 8 months and in the cerebellum at 18 months. In the cerebellum, it decreased the density of microglia in GFAP-IL6 mice to a similar level after 5 and 15 months' feeding. Tenilsetam prevented the volume loss of the cerebellum at 8 months. It also significantly decreased TNF-α in the cerebellum of GFAP-IL6 mice to a similar level of WT mice after 15 months of feeding. CONCLUSION: Tenilsetam has anti-inflammatory effects evidenced by the decreased number of microglia in both the cerebellum and hippocampus, and decreased TNF-α levels in the GFAP-IL6 Tenilsetam fed animals.

Novel promising therapeutics against chronic neuroinflammation and neurodegeneration in Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder, characterized by deposition of amyloid plaques and neurofibrillary tangles, as well as microglial and astroglial activation, and, finally, leading to neuronal dysfunction and death. Current treatments for AD primarily focus on enhancement of cholinergic transmission. However, these treatments are only symptomatic, and no disease-modifying drug is available for the treatment of AD patients. This review will provide an overview of the antioxidant, anti-inflammatory, anti-amyloidogenic, neuroprotective, and cognition-enhancing effects of a variety of nutraceuticals including curcumin, apigenin, docosahexaenoic acid, epigallocatechin gallate, α-lipoic acid and resveratrol and their potential for AD prevention and treatment. We suggest that therapeutic use of these compounds might lead to a safe strategy to delay the onset of AD or slow down its progression. The continuing investigation of the potential of these substances is necessary as they are promising compounds to yield a possible remedy for this pervasive disease.

Use of non-pharmaceutical interventions to reduce the transmission of influenza in adults: A systematic review.

During seasonal influenza epidemics and pandemics, virus transmission causes significant public health concern. Reduction of viral transmission by non-pharmaceutical interventions (NPI) has a significant appeal and is often recommended. However, the efficacy of such interventions is unclear. A systematic literature review was undertaken to identify and evaluate the published literature on NPI efficacy to prevent human transmission of influenza virus in adults. Reviewers assessed the quality of eligible studies utilizing the Critical Appraisal Skills Programme for bias and the Scottish Intercollegiate Guidelines Network for methodological quality. Studies were assessed for risk of bias domains of random sequence generation, allocation concealment, attribution bias, selective reporting and blinding. Relevant citations of 2247 were reduced to 100 for full-text evaluation. Only seven met all selection criteria and pooled analysis was not feasible. Of the seven studies, two were randomized controlled trials (RCT) and five were cluster RCT. The main NPI studied were disinfection and hygiene; barriers; and combined NPI. However, these seven RCT had significant design flaws. Only two studies used laboratory confirmed influenza and poor statistical power was a major problem. Positive significant interventions included professional oral hygiene intervention in the elderly and hand washing. Despite the potential for NPI in preventing influenza transmission, there is very limited data available. Hand washing and dental hygiene may be useful, but other interventions have not been fully assessed. Properly designed studies evaluating large populations including 'at risk' patients and in a variety of communities are needed.

A review of the effectiveness of psychological interventions used for anxiety and depression in chronic obstructive pulmonary disease.

BACKGROUND: Anxiety and depression are recognised co-morbidities associated with COPD and have been related to poor health outcomes. Therapies to relieve anxiety and depression are currently not detailed in clinical guidelines. METHODS: A systematic review of psychological interventions for anxiety and depression in adults with COPD was conducted. Meta-analysis utilising the random effects model was undertaken for 4 studies that employed the same psychological intervention type, Cognitive Behavioural Therapy (CBT). RESULTS: Seven studies met the inclusion criteria. Four studies used CBT. Included studies utilised psychotherapy, uncertainty management and minimal psychological therapy. 70% of participants were male. Many studies had poor methodological quality. The meta-analysis showed a small decrease in symptoms for both anxiety (SMD -0.49, 95% CI -1.04, 0.06, P=0.08, n=193) and depression (SMD -0.37, 95% CI -0.86, 0.11, P=0.13, n=193). No change occurred when sensitivity analyses were conducted. CONCLUSION: Anxiety and depression in COPD patients are known to impact on health outcomes. Effective psychological interventions such as CBT may assist people with COPD in reducing psychological burden. There remains a need for well-designed studies to provide substantive evidence for the use of psychological interventions in this patient population.

Chronic neuroinflammation in Alzheimer's disease: new perspectives on animal models and promising candidate drugs.

Chronic neuroinflammation is now considered one of the major factors in the pathogenesis of Alzheimer's disease (AD). However, the most widely used transgenic AD models (overexpressing mutated forms of amyloid precursor protein, presenilin, and/or tau) do not demonstrate the degree of inflammation, neurodegeneration (particularly of the cholinergic system), and cognitive decline that is comparable with the human disease. Hence a more suitable animal model is needed to more closely mimic the resulting cognitive decline and memory loss in humans in order to investigate the effects of neuroinflammation on neurodegeneration. One of these models is the glial fibrillary acidic protein-interleukin 6 (GFAP-IL6) mouse, in which chronic neuroinflammation triggered constitutive expression of the cytokine interleukin-6 (IL-6) in astrocytes. These transgenic mice show substantial and progressive neurodegeneration as well as a decline in motor skills and cognitive function, starting from 6 months of age. This animal model could serve as an excellent tool for drug discovery and validation in vivo. In this review, we have also selected three potential anti-inflammatory drugs, curcumin, apigenin, and tenilsetam, as candidate drugs, which could be tested in this model.