S100A8-enriched microglia populate the brain of tau-seeded and accelerated aging mice.

Autor: Gruel R; Laboratory of Cell Biology & Histology, University of Antwerp, Wilrijk, Belgium., Bijnens B; Microglia and Inflammation in Neurological Disorders (MIND) Lab, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium.; Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium., Van Den Daele J; Laboratory of Cell Biology & Histology, University of Antwerp, Wilrijk, Belgium., Thys S; Laboratory of Cell Biology & Histology, University of Antwerp, Wilrijk, Belgium., Willems R; Janssen Research and Development, Neuroscience Therapeutic Area, Beerse, Belgium., Wuyts D; Janssen Research and Development, Neuroscience Therapeutic Area, Beerse, Belgium., Van Dam D; Laboratory of Neurochemistry & Behaviour, Experimental Neurobiology Unit, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.; Department of Neurology and Alzheimer Center, University of Groningen, Groningen, The Netherlands., Verstraelen P; Laboratory of Cell Biology & Histology, University of Antwerp, Wilrijk, Belgium., Verboven R; Laboratory of Cell Biology & Histology, University of Antwerp, Wilrijk, Belgium., Roels J; VIB Single Cell Core, VIB, Ghent-Leuven, Belgium.; VIB-UGent Center for Inflammation Research, Ghent, Belgium., Vandamme N; VIB Single Cell Core, VIB, Ghent-Leuven, Belgium.; VIB-UGent Center for Inflammation Research, Ghent, Belgium., Mancuso R; Microglia and Inflammation in Neurological Disorders (MIND) Lab, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium.; Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium., Pita-Almenar JD; Janssen Research and Development, Neuroscience Therapeutic Area, Beerse, Belgium., De Vos WH; Laboratory of Cell Biology & Histology, University of Antwerp, Wilrijk, Belgium.; Antwerp Centre for Advanced Microscopy, University of Antwerp, Antwerp, Belgium.; μNEURO research excellence consortium, University of Antwerp, Antwerp, Belgium.
Jazyk: angličtina
Zdroj: Aging cell [Aging Cell] 2024 May; Vol. 23 (5), pp. e14120. Date of Electronic Publication: 2024 Feb 25.
DOI: 10.1111/acel.14120
Abstrakt: Long considered to fluctuate between pro- and anti-inflammatory states, it has now become evident that microglia occupy a variegated phenotypic landscape with relevance to aging and neurodegeneration. However, whether specific microglial subsets converge in or contribute to both processes that eventually affect brain function is less clear. To investigate this, we analyzed microglial heterogeneity in a tauopathy mouse model (K18-seeded P301L) and an accelerated aging model (Senescence-Accelerated Mouse-Prone 8, SAMP8) using cellular indexing of transcriptomes and epitopes by sequencing. We found that widespread tau pathology in K18-seeded P301L mice caused a significant change in the number and morphology of microglia, but only a mild overrepresentation of disease-associated microglia. At the cell population-level, we observed a marked upregulation of the calprotectin-encoding genes S100a8 and S100a9. In 9-month-old SAMP8 mice, we identified a unique microglial subpopulation that showed partial similarity with the disease-associated microglia phenotype and was additionally characterized by a high expression of the same calprotectin gene set. Immunostaining for S100A8 revealed that this population was enriched in the hippocampus, correlating with the cognitive impairment observed in this model. However, incomplete colocalization between their residence and markers of neuronal loss suggests regional specificity. Importantly, S100A8-positive microglia were also retrieved in brain biopsies of human AD and tauopathy patients as well as in a biopsy of an aged individual without reported pathology. Thus, the emergence of S100A8-positive microglia portrays a conspicuous commonality between accelerated aging and tauopathy progression, which may have relevance for ensuing brain dysfunction.
(© 2024 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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