TREM2 regulates microglial cell activation in response to demyelination in vivo

Abstract Microglia are phagocytic cells that survey the brain and perform neuroprotective functions in response to tissue damage, but their activating receptors are largely unknown. Triggering receptor expressed on myeloid cells 2 (TREM2) is a microglial immunoreceptor whose loss-of-function mutations in humans cause presenile dementia, while genetic variants are associated with increased risk of neurodegenerative diseases. In myeloid cells, TREM2 has been involved in the regulation of phagocytosis, cell proliferation and inflammatory responses in vitro. However, it is unknown how TREM2 contributes to microglia function in vivo. Here, we identify a critical role for TREM2 in the activation and function of microglia during cuprizone (CPZ)-induced demyelination. TREM2-deficient (TREM2−/−) mice had defective clearance of myelin debris and more axonal pathology, resulting in impaired clinical performances compared to wild-type (WT) mice. TREM2−/− microglia proliferated less in areas of demyelination and were less activated, displaying a more resting morphology and decreased expression of the activation markers MHC II and inducible nitric oxide synthase as compared to WT. Mechanistically, gene expression and ultrastructural analysis of microglia suggested a defect in myelin degradation and phagosome processing during CPZ intoxication in TREM2−/− microglia. These findings place TREM2 as a key regulator of microglia activation in vivo in ...
Source: Acta Neuropathologica - Category: Neurology Source Type: research

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Publication date: Available online 13 October 2019Source: Alzheimer's &DementiaAuthor(s): Catherine M. Calvin, Tim Wilkinson, John M. Starr, Cathie Sudlow, Saskia P. Hagenaars, Sarah E. Harris, Christian Schnier, Gail Davies, Chloe Fawns-Ritchie, Catharine R. Gale, John Gallacher, Ian J. DearyAbstractIntroductionProspective studies reporting associations between cognitive performance and subsequent incident dementia have been subject to attrition bias. Furthermore, the extent to which established risk factors account for such associations requires further elucidation.MethodsWe used UK Biobank baseline cognitive data (n...
Source: Alzheimer's and Dementia: The Journal of the Alzheimer's Association - Category: Geriatrics Source Type: research
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Source: the Mail online | Health - Category: Consumer Health News Source Type: news
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Source: Frontiers in Neurology - Category: Neurology Source Type: research
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Source: Reuters: Health - Category: Consumer Health News Tags: healthNews Source Type: news
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Source: Washington Post: To Your Health - Category: Consumer Health News Authors: Source Type: news
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Source: - Category: Consumer Health News Source Type: news
Commentary on "Low Mood and Risk of Dementia: The Role of Marital Status and Living Situation". Am J Geriatr Psychiatry. 2019 Sep 11;: Authors: Monin JK PMID: 31606276 [PubMed - as supplied by publisher]
Source: The American Journal of Geriatric Psychiatry - Category: Psychiatry Tags: Am J Geriatr Psychiatry Source Type: research
Authors: Iliffe S, Gallo JJ PMID: 31606275 [PubMed - as supplied by publisher]
Source: The American Journal of Geriatric Psychiatry - Category: Psychiatry Tags: Am J Geriatr Psychiatry Source Type: research
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Source: Journal of the American Medical Directors Association - Category: Health Management Authors: Tags: Research Letter Source Type: research
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Source: Minding Our Elders - Category: Geriatrics Authors: Source Type: blogs
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