Journal ArticleDOI
Synaptic Pruning by Microglia Is Necessary for Normal Brain Development
Rosa C. Paolicelli,Giulia Bolasco,Francesca Pagani,Laura Maggi,Maria Scianni,Patrizia Panzanelli,Maurizio Giustetto,Tiago Ferreira,Eva Guiducci,Laura Dumas,Davide Ragozzino,Cornelius Gross +11 more
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TLDR
It is shown that microglia actively engulf synaptic material and play a major role in synaptic pruning during postnatal development in mice and this work suggests that deficits in microglian function may contribute to synaptic abnormalities seen in some neurodevelopmental disorders.Abstract:
Microglia are highly motile phagocytic cells that infiltrate and take up residence in the developing brain, where they are thought to provide a surveillance and scavenging function. However, although microglia have been shown to engulf and clear damaged cellular debris after brain insult, it remains less clear what role microglia play in the uninjured brain. Here, we show that microglia actively engulf synaptic material and play a major role in synaptic pruning during postnatal development in mice. These findings link microglia surveillance to synaptic maturation and suggest that deficits in microglia function may contribute to synaptic abnormalities seen in some neurodevelopmental disorders.read more
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Macrophage biology in development, homeostasis and disease
TL;DR: This Review discusses how macrophage regulate normal physiology and development, and provides several examples of their pathophysiological roles in disease, and defines the ‘hallmarks’ of macrophages according to the states that they adopt during the performance of their various roles.
Journal ArticleDOI
Physiology of Microglia
TL;DR: Current studies indicate that even in the normal brain, microglia have highly motile processes by which they scan their territorial domains, and microglial cells are considered the most susceptible sensors of brain pathology.
Journal ArticleDOI
Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner.
Dorothy P. Schafer,Emily K. Lehrman,Amanda G. Kautzman,Ryuta Koyama,Alan R. Mardinly,Ryo Yamasaki,Richard M. Ransohoff,Michael E. Greenberg,Ben A. Barres,Beth Stevens +9 more
TL;DR: It is shown that microglia engulf presynaptic inputs during peak retinogeniculate pruning and that engulfment is dependent upon neural activity and themicroglia-specific phagocytic signaling pathway, complement receptor 3(CR3)/C3.
Journal ArticleDOI
Neuropathological Alterations in Alzheimer Disease
TL;DR: Postmortem studies have enabled the staging of the progression of both amyloid and tangle pathologies, and the development of diagnostic criteria that are now used worldwide, and these cross-sectional neuropathological data have been largely validated by longitudinal in vivo studies using modern imaging biomarkers such as amyloids PET and volumetric MRI.
Journal ArticleDOI
Identification of a unique TGF-β–dependent molecular and functional signature in microglia
Oleg Butovsky,Mark P. Jedrychowski,Craig S. Moore,Ron Cialic,Amanda J. Lanser,Galina Gabriely,Thomas Koeglsperger,Ben Dake,Pauline M. Wu,Camille Doykan,Zain Fanek,LiPing Liu,Zhuoxun Chen,Jeffrey D. Rothstein,Richard M. Ransohoff,Steven P. Gygi,Jack P. Antel,Howard L. Weiner +17 more
TL;DR: It is found that TGF-β was required for the in vitro development of microglia that express the microglial molecular signature characteristic of adultmicroglia and that microglian were absent in the CNS of TGF -β1–deficient mice.
References
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Journal ArticleDOI
Resting Microglial Cells Are Highly Dynamic Surveillants of Brain Parenchyma in Vivo
TL;DR: Using in vivo two-photon imaging in neocortex, it is found that microglial cells are highly active in their presumed resting state, continually surveying their microenvironment with extremely motile processes and protrusions.
Journal ArticleDOI
Fate Mapping Analysis Reveals That Adult Microglia Derive from Primitive Macrophages
Florent Ginhoux,Florent Ginhoux,Melanie Greter,Marylene Leboeuf,Sayan Nandi,Peter See,Solen Gokhan,Mark F. Mehler,Simon J. Conway,Lai Guan Ng,E. Richard Stanley,Igor M. Samokhvalov,Miriam Merad +12 more
TL;DR: Results identify microglia as an ontogenically distinct population in the mononuclear phagocyte system and have implications for the use of embryonically derived microglial progenitors for the treatment of various brain disorders.
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ATP mediates rapid microglial response to local brain injury in vivo
Dimitrios Davalos,Jaime Grutzendler,Jaime Grutzendler,Guang Yang,Jiyun Kim,Yi Zuo,Steffen Jung,Dan R. Littman,Michael L. Dustin,Wen-Biao Gan +9 more
TL;DR: Extracellular ATP regulates microglial branch dynamics in the intact brain, and its release from the damaged tissue and surrounding astrocytes mediates a rapid microglia response towards injury.
Journal ArticleDOI
Microglia: active sensor and versatile effector cells in the normal and pathologic brain
TL;DR: This review focuses on several key observations that illustrate the multi-faceted activities of microglia in the normal and pathologic brain.
Journal ArticleDOI
The classical complement cascade mediates CNS synapse elimination.
Beth Stevens,Nicola J. Allen,Luis E. Vazquez,Gareth R. Howell,Karen S. Christopherson,Navid Nouri,Kristina D. Micheva,Adrienne K. Mehalow,Andrew D. Huberman,Benjamin K. Stafford,Alexander Sher,Alan Litke,John D. Lambris,Stephen J. Smith,Simon W. M. John,Ben A. Barres +15 more
TL;DR: It is shown that C1q, the initiating protein in the classical complement cascade, is expressed by postnatal neurons in response to immature astrocytes and is localized to synapses throughout the postnatal CNS and retina, supporting a model in which unwanted synapses are tagged by complement for elimination and suggesting that complement-mediated synapse elimination may become aberrantly reactivated in neurodegenerative disease.