Microglia turnover with aging and in an Alzheimer's model via long-term in vivo single-cell imaging

• Published in: Nature neuroscience Vol. 20; no. 10; pp. 1371 - 1376
• Main Authors: Füger, Petra, Hefendehl, Jasmin K, Veeraraghavalu, Karthik, Wendeln, Ann-Christin, Schlosser, Christine, Obermüller, Ulrike, Wegenast-Braun, Bettina M, Neher, Jonas J, Martus, Peter, Kohsaka, Shinichi, Thunemann, Martin, Feil, Robert, Sisodia, Sangram S, Skodras, Angelos, Jucker, Mathias
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.10.2017; Nature Publishing Group
• Subjects: 14; 14/34; 14/35; 14/69; 631/378; 631/378/371; 64; 64/110; 64/60; Aging; Aging (artificial); Aging (Biology); Aging - physiology; Alzheimer Disease - pathology; Alzheimer Disease - physiopathology; Alzheimer's disease; Amyloidosis; Animal Genetics and Genomics; Animals; Behavioral Sciences; Biological Techniques; Biomedicine; Brain; Cell Death; Cell Proliferation; Complications and side effects; Genetic aspects; Homeostasis; Kaplan-Meier Estimate; Life span; Lifetime; Mice; Mice, Transgenic; Microglia; Microglia - cytology; Microglia - pathology; Microglia - physiology; Microscopy; Microscopy, Fluorescence, Multiphoton; Neocortex; Neocortex - physiology; Neurobiology; Neurodegenerative diseases; Neuroimaging; Neurological diseases; Neurosciences; Physiological aspects; Plaque, Amyloid - pathology; Priming; Rodents; Senescence; Single-Cell Analysis; Transgenic animals; United States; Germany
• ISSN: 1097-6256; 1546-1726
• DOI: 10.1038/nn.4631

Neocortical resident microglia are long-lived cells. Füger et al . report that approximately half of these cells survive for the entire lifespan of a mouse. While microglial proliferation under homeostatic conditions is low, proliferation is increased in a mouse model of Alzheimer's disease. To clarify the role of microglia in brain homeostasis and disease, an understanding of their maintenance, proliferation and turnover is essential. The lifespan of brain microglia, however, remains uncertain, and reflects confounding factors in earlier assessments that were largely indirect. We genetically labeled single resident microglia in living mice and then used multiphoton microscopy to monitor these cells over time. Under homeostatic conditions, we found that neocortical resident microglia were long-lived, with a median lifetime of well over 15 months; thus, approximately half of these cells survive the entire mouse lifespan. While proliferation of resident neocortical microglia under homeostatic conditions was low, microglial proliferation in a mouse model of Alzheimer's β-amyloidosis was increased threefold. The persistence of individual microglia throughout the mouse lifespan provides an explanation for how microglial priming early in life can induce lasting functional changes and how microglial senescence may contribute to age-related neurodegenerative diseases.