Journal ArticleDOI
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
TLDR
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.Abstract:
Parenchymal microglia are the principal immune cells of the brain. Time-lapse two-photon imaging of GFP-labeled microglia demonstrates that the fine termini of microglial processes are highly dynamic in the intact mouse cortex. Upon traumatic brain injury, microglial processes rapidly and autonomously converge on the site of injury without cell body movement, establishing a potential barrier between the healthy and injured tissue. This rapid chemotactic response can be mimicked by local injection of ATP and can be inhibited by the ATP-hydrolyzing enzyme apyrase or by blockers of G protein-coupled purinergic receptors and connexin channels, which are highly expressed in astrocytes. The baseline motility of microglial processes is also reduced significantly in the presence of apyrase and connexin channel inhibitors. Thus, extracellular ATP regulates microglial branch dynamics in the intact brain, and its release from the damaged tissue and surrounding astrocytes mediates a rapid microglial response towards injury.read more
Citations
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Deep tissue two-photon microscopy
Fritjof Helmchen,Winfried Denk +1 more
TL;DR: Fundamental concepts of nonlinear microscopy are reviewed and conditions relevant for achieving large imaging depths in intact tissue are discussed.
Journal ArticleDOI
Microglia-mediated neurotoxicity: uncovering the molecular mechanisms
TL;DR: Overactivated microglia can be detected using imaging techniques and therefore this knowledge offers an opportunity not only for early diagnosis but, importantly, for the development of targeted anti-inflammatory therapies that might slow or halt the progression of neurodegenerative disease.
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
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
TL;DR: 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.
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.
References
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TL;DR: An understanding of intercellular signalling pathways for microglia proliferation and activation could form a rational basis for targeted intervention on glial reactions to injuries in the CNS.
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Analysis of fractalkine receptor CX(3)CR1 function by targeted deletion and green fluorescent protein reporter gene insertion.
Steffen Jung,Julio Aliberti,Petra Graemmel,Mary Jean Sunshine,Georg W. Kreutzberg,Alan Sher,Dan R. Littman +6 more
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Signal transduction via P2-purinergic receptors for extracellular ATP and other nucleotides
TL;DR: Current research in this area is directed toward the identification and structural characterization of nucleotide or P2-purinergic receptors that are activated when ATP or other nucleotides are bound.
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Long-term dendritic spine stability in the adult cortex
TL;DR: It is shown that filopodia-like dendritic protrusions, extending and retracting over hours, are abundant in young animals but virtually absent from the adult, providing a potential structural basis for long-term information storage.
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Microglia as mediators of inflammatory and degenerative diseases.
TL;DR: The role of microglia in three diseases in which their activity is at least partially deleterious: HIV, multiple sclerosis, and Alzheimer's disease is discussed in this article, where the authors discuss their role in protecting the central nervous system.