Emerging roles of astrocytes in neural circuit development
Laura E. Clarke,Ben A. Barres +1 more
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TLDR
A better understanding of how astrocytes regulate neural circuit development and function in the healthy and diseased brain might lead to the development of therapeutic agents to treat these diseases.Abstract:
Astrocytes are now emerging as key participants in many aspects of brain development, function and disease. In particular, new evidence shows that astrocytes powerfully control the formation, maturation, function and elimination of synapses through various secreted and contact-mediated signals. Astrocytes are also increasingly being implicated in the pathophysiology of many psychiatric and neurological disorders that result from synaptic defects. A better understanding of how astrocytes regulate neural circuit development and function in the healthy and diseased brain might lead to the development of therapeutic agents to treat these diseases.read more
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Journal ArticleDOI
Neurotoxic reactive astrocytes are induced by activated microglia
Shane A. Liddelow,Kevin A. Guttenplan,Laura E. Clarke,Frederick C. Bennett,Christopher J. Bohlen,Lucas Schirmer,Mariko L. Bennett,Alexandra E. Münch,Won-Suk Chung,Todd C. Peterson,Daniel K. Wilton,Arnaud Frouin,Brooke A. Napier,Nikhil Panicker,Manoj Kumar,Marion S. Buckwalter,David H. Rowitch,Valina L. Dawson,Ted M. Dawson,Beth Stevens,Ben A. Barres +20 more
TL;DR: It is shown that activated microglia induce A1 astrocytes by secreting Il-1α, TNF and C1q, and that these cytokines together are necessary and sufficient to induce A2 astroCytes, which are abundant in various human neurodegenerative diseases.
Journal ArticleDOI
Purification and Characterization of Progenitor and Mature Human Astrocytes Reveals Transcriptional and Functional Differences with Mouse.
Ye Zhang,Steven A. Sloan,Laura E. Clarke,Christine Caneda,Colton A. Plaza,Paul D. Blumenthal,Hannes Vogel,Gary K. Steinberg,Michael S. B. Edwards,Gordon Li,John A. Duncan,Samuel H. Cheshier,Lawrence M. Shuer,Edward F. Chang,Gerald A. Grant,Melanie Hayden Gephart,Ben A. Barres +16 more
TL;DR: The development of an immunopanning method to acutely purify astrocytes from fetal, juvenile, and adult human brains and to maintain these cells in serum-free cultures is reported, finding that human astroCytes have abilities similar to those of murine astroicytes in promoting neuronal survival, inducing functional synapse formation, and engulfing synaptosomes.
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Microglia emerge as central players in brain disease.
Michael W. Salter,Beth Stevens +1 more
TL;DR: Recent developments in the rapidly expanding understanding of the function, as well as the dysfunction, of microglia in disorders of the CNS are focused on.
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Establishment and Dysfunction of the Blood-Brain Barrier
TL;DR: The mechanisms regulating the formation and maintenance of the BBB and functions of BBB-associated cell types are examined and the growing evidence associating BBB breakdown with the pathogenesis of inherited monogenic neurological disorders and complex multifactorial diseases, including Alzheimer's disease is discussed.
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The intersection of amyloid beta and tau at synapses in Alzheimer’s disease
TL;DR: It is suggested that synaptic changes are central to the disease process, and that the march of neurofibrillary tangles through brain circuits appears to take advantage of recently described mechanisms of transsynaptic spread of pathological forms of tau.
References
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Synaptic Activity and the Construction of Cortical Circuits
Lawrence C. Katz,Carla J. Shatz +1 more
TL;DR: The sequential combination of spontaneously generated and experience-dependent neural activity endows the brain with an ongoing ability to accommodate to dynamically changing inputs during development and throughout life.
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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
A transcriptome database for astrocytes, neurons, and oligodendrocytes: a new resource for understanding brain development and function.
John D. Cahoy,Ben Emery,Amit Kaushal,Lynette C. Foo,Jennifer L. Zamanian,Karen S. Christopherson,Yi Xing,Jane L. Lubischer,Paul A. Krieg,Sergey A. Krupenko,Wesley J. Thompson,Ben A. Barres +11 more
TL;DR: These findings call into question the concept of a “glial” cell class as the gene profiles of astrocyte and oligodendrocytes are as dissimilar to each other as they are to neurons, for better understanding of neural development, function, and disease.
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.
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Long-term in vivo imaging of experience-dependent synaptic plasticity in adult cortex
Joshua T. Trachtenberg,Brian E. Chen,Graham Knott,Guoping Feng,Joshua R. Sanes,Egbert Welker,Karel Svoboda +6 more
TL;DR: The measurements suggest that sensory experience drives the formation and elimination of synapses and that these changes might underlie adaptive remodelling of neural circuits.
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Neurotoxic reactive astrocytes are induced by activated microglia
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