Neuroinvasion of SARS-CoV-2 in human and mouse brain

The Journal of Experimental Medicine, Journal Year: 2021, Volume and Issue: 218(3)

Published: Jan. 12, 2021

Although COVID-19 is considered to be primarily a respiratory disease, SARS-CoV-2 affects multiple organ systems including the central nervous system (CNS). Yet, there no consensus on consequences of CNS infections. Here, we used three independent approaches probe capacity infect brain. First, using human brain organoids, observed clear evidence infection with accompanying metabolic changes in infected and neighboring neurons. However, for type I interferon responses was detected. We demonstrate that neuronal can prevented by blocking ACE2 antibodies or administering cerebrospinal fluid from patient. Second, mice overexpressing ACE2, neuroinvasion vivo. Finally, autopsies patients who died COVID-19, detect cortical neurons note pathological features associated minimal immune cell infiltrates. These results provide neuroinvasive an unexpected consequence direct SARS-CoV-2.

Language: Английский

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Brain organoids: advances, applications and challenges

Development, Journal Year: 2019, Volume and Issue: 146(8)

Published: April 15, 2019

Brain organoids are self-assembled three-dimensional aggregates generated from pluripotent stem cells with cell types and cytoarchitectures that resemble the embryonic human brain. As such, they have emerged as novel model systems can be used to investigate brain development disorders. Although mimic many key features of early at molecular, cellular, structural functional levels, some aspects development, such formation distinct cortical neuronal layers, gyrification, establishment complex circuitry, not fully recapitulated. Here, we summarize recent advances in organoid methodologies discuss their applications disease modeling. In addition, compare current brain, highlighting currently cannot recapitulated, perspectives for advancing technologies expand applications.

Language: Английский

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Cerebral organoids at the air–liquid interface generate diverse nerve tracts with functional output

Nature Neuroscience, Journal Year: 2019, Volume and Issue: 22(4), P. 669 - 679

Published: March 18, 2019

Language: Английский

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Sliced Human Cortical Organoids for Modeling Distinct Cortical Layer Formation

Cell stem cell, Journal Year: 2020, Volume and Issue: 26(5), P. 766 - 781.e9

Published: March 9, 2020

Language: Английский

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Modeling Alzheimer’s disease with iPSC-derived brain cells

Molecular Psychiatry, Journal Year: 2019, Volume and Issue: 25(1), P. 148 - 167

Published: Aug. 7, 2019

Alzheimer’s disease is a devastating neurodegenerative disorder with no cure. Countless promising therapeutics have shown efficacy in rodent models yet failed to benefit human patients. While hope remains that earlier intervention existing will improve outcomes, it becoming increasingly clear new approaches understand and combat the pathophysiology of are needed. Human induced pluripotent stem cell (iPSC) technologies changed face preclinical research iPSC-derived types being utilized study an array conditions, including disease. All major brain can now be differentiated from iPSCs, while complex co-culture systems developed facilitate neuroscience research. Many cellular functions perturbed recapitulated using cells vitro, platforms beginning yield insights into interactions occur between during neurodegeneration. Further, iPSC-based genome editing tools critical understanding roles numerous genes mutations found modify risk past decade. still their relative infancy, these developing hold considerable promise push forward efforts other disorders.

Language: Английский

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Development and Arealization of the Cerebral Cortex

Neuron, Journal Year: 2019, Volume and Issue: 103(6), P. 980 - 1004

Published: Sept. 1, 2019

Language: Английский

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New insights into the development of the human cerebral cortex

Journal of Anatomy, Journal Year: 2019, Volume and Issue: 235(3), P. 432 - 451

Published: Aug. 2, 2019

The cerebral cortex constitutes more than half the volume of human brain and is presumed to be responsible for neuronal computations underlying complex phenomena, such as perception, thought, language, attention, episodic memory voluntary movement. Rodent models are extremely valuable investigation development, but cannot provide insight into aspects that unique or highly derived in humans. Many psychiatric neurological conditions have developmental origins studied adequately animal models. has some genetic, molecular, cellular anatomical features, which need further explored. Anatomical Society devoted its summer meeting topic Human Brain Development June 2018 tackle these important issues. was organized by Gavin Clowry (Newcastle University) Zoltán Molnár (University Oxford), held at St John's College, Oxford. participants provided a broad overview structure context scaling relationships across brains mammals, conserved principles recent changes lineage. Speakers considered how progenitors diversified generate an increasing variety cortical neurons. formation earliest circuits generated neurons subplate discussed together with their involvement neurodevelopmental pathologies. Gene expression networks susceptibility genes associated diseases were compared can identified organoids developed from induced pluripotent stem cells recapitulate vivo development. New views on specification glutamatergic pyramidal γ-aminobutyric acid (GABA)ergic interneurons. With advancement various imaging methods, histopathological observations now linked normal diseases. Our review gives general evaluation exciting new developments areas. much enlarged association greater interconnectivity areas each other expanded thalamus. relative enlargement upper layers, enhanced diversity function inhibitory interneurons transient layer during Here we highlight studies address differences emerge development focusing diverse facets our evolution.

Language: Английский

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Disease modelling in human organoids

Disease Models & Mechanisms, Journal Year: 2019, Volume and Issue: 12(7)

Published: July 1, 2019

ABSTRACT The past decade has seen an explosion in the field of vitro disease modelling, particular development organoids. These self-organizing tissues derived from stem cells provide a unique system to examine mechanisms ranging organ homeostasis and disease. Because organoids develop according intrinsic developmental programmes, resultant tissue morphology recapitulates architecture with remarkable fidelity. Furthermore, fact that these can be human progenitors allows for study uniquely processes disorders. This article accompanying poster highlight currently available methods, particularly those aimed at modelling biology, overview their capabilities limitations. We also speculate on possible future technological advances have potential great strides both regenerative strategies.

Language: Английский

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Building Models of Brain Disorders with Three-Dimensional Organoids

Neuron, Journal Year: 2018, Volume and Issue: 100(2), P. 389 - 405

Published: Oct. 1, 2018

Language: Английский

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A materials-science perspective on tackling COVID-19

Nature Reviews Materials, Journal Year: 2020, Volume and Issue: 5(11), P. 847 - 860

Published: Oct. 14, 2020

The ongoing SARS-CoV-2 pandemic highlights the importance of materials science in providing tools and technologies for antiviral research treatment development. In this Review, we discuss previous efforts developing imaging systems microfluidic devices in-depth real-time investigation viral structures transmission, as well material platforms detection viruses delivery drugs vaccines. We highlight contribution to manufacturing personal protective equipment design simple, accurate low-cost virus-detection devices. then investigate future possibilities development, examining role antiviral-drug design, including synthetic organoids organs-on-a-chip, drug vaccination, production medical equipment. Materials-science-based not only contribute but can also provide understanding, protection, diseases. Materials provides protection against infections, diagnosis, prevention This Review discusses present directions materials-science research, with a focus on COVID-19.

Language: Английский

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