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The Microbial Assay for Risk Assessment (MARA) is an innovative system based on an array of eleven different microbial species freeze-dried in a 96 well micro-titre plate format. Developed for testing the toxicity of chemicals, mixtures and environmental samples, the assay employs species of a taxonomically diverse range. In addition to ten prokaryotic species, a eukaryote (yeast) is included in the range. The MARA's innate scope of a multi-dimensional test allows determination of toxicity based on a unique assay multi-dimensional fingerprint or index and numerically expressed as the mean Microbial Toxic Concentration (MTC). The most significant potential of this low-cost test is in the additional inference that can be conveyed to the toxicity evaluation because of the presence of each of the eleven different constituent species. In view of the fact that conventional aquatic bioassays, like fish or cladoceran tests, are expensive and unpractical, the MARA could provide a cost-effective solution for routine ecotoxicological testing/screening programmes. The performance of the MARA was evaluated to ascertain its capability and potential scope. Sensitivity to toxicants and different environmental samples was assessed. Evaluation included comparison with other tests; namely Microtox®, invertebrate (Daphnia magna and Thamnocephalus platyurus) microbiotests, and conventional respiration- and nitrification-inhibition tests. The inference of the evaluation implemented concluded that MARA is a useful tool for ecotoxicity testing of aquatic and terrestrial environments. MARA's performance further assessed with the implementation of an international inter-laboratory trial indicated that performance of the assay was satisfactory and the results were within the acceptable range. MARA is a robust multi-species assay offering scope for toxicity assessment of a diverse range of samples. [ABSTRACT FROM AUTHOR]

Background: Neuropathologically, synapse loss correlates most strongly with the progressive cognitive decline observed in Alzheimer’s disease (AD). Despite strong evidence from genetic studies implicating changes in glia as important for disease risk, we are only beginning to understand the role that microglia and astrocytes play in synapse degeneration in AD. Method: In this study, we have used high resolution imaging of post‐mortem brain tissue to examine whether glia contain synaptic proteins in AD. Cultures of primary mouse and human microglia were exposed to pHrodo‐tagged synapses from human AD or control post‐mortem brain for phagocytosis assays. Mouse models expressing AD associated genes were used for RNA sequencing and translating ribosomal affinity purification (TRAP) followed by RNA sequencing. Result: We observe both astrocytes and microglia contain synaptic proteins in human AD more than in control brain. Cultured microglia phagocytose synapses from AD brain more and faster than those from control brain. RNA sequencing in AD model mice revealed strong increases neuroinflammatory signals including transcripts expressed in microglia and astrocytes and decreases in transcripts related to synaptic function. When examining the astrocyte specific changes with TRAP, we observed increases in phagosome and lysosome related pathways. Conclusion: Together, our results indicate that microglia and astrocytes play a role in synapse degeneration or clearance of dead synapses in Alzheimer’s disease. [ABSTRACT FROM AUTHOR]