Blood–brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders

Nature Reviews Neurology, Journal Year: 2018, Volume and Issue: 14(3), P. 133 - 150

Published: Jan. 29, 2018

Language: Английский

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The Neurovascular Unit Coming of Age: A Journey through Neurovascular Coupling in Health and Disease

Neuron, Journal Year: 2017, Volume and Issue: 96(1), P. 17 - 42

Published: Sept. 1, 2017

Language: Английский

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Blood-Brain Barrier: From Physiology to Disease and Back

Physiological Reviews, Journal Year: 2018, Volume and Issue: 99(1), P. 21 - 78

Published: Oct. 3, 2018

The blood-brain barrier (BBB) prevents neurotoxic plasma components, blood cells, and pathogens from entering the brain. At same time, BBB regulates transport of molecules into out central nervous system (CNS), which maintains tightly controlled chemical composition neuronal milieu that is required for proper functioning. In this review, we first examine molecular cellular mechanisms underlying establishment BBB. Then, focus on physiology, endothelial pericyte transporters, perivascular paravascular transport. Next, discuss rare human monogenic neurological disorders with primary genetic defect in BBB-associated cells demonstrating link between breakdown neurodegeneration. review effects genes inheritance and/or increased susceptibility Alzheimer's disease (AD), Parkinson's (PD), Huntington's disease, amyotrophic lateral sclerosis (ALS) relation to other pathologies deficits. We next how dysfunction relates deficits majority sporadic AD, PD, ALS cases, multiple sclerosis, neurodegenerative disorders, acute CNS such as stroke, traumatic brain injury, spinal cord epilepsy. Lastly, BBB-based therapeutic opportunities. conclude lessons learned future directions, emphasis technological advances investigate functions living brain, at level, address key unanswered questions.

Language: Английский

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A molecular atlas of cell types and zonation in the brain vasculature

Nature, Journal Year: 2018, Volume and Issue: 554(7693), P. 475 - 480

Published: Feb. 13, 2018

Language: Английский

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Single-cell profiling of the developing mouse brain and spinal cord with split-pool barcoding

Science, Journal Year: 2018, Volume and Issue: 360(6385), P. 176 - 182

Published: March 15, 2018

Identifying single-cell types in the mouse brain The recent development of genomic techniques allows us to profile gene expression at level easily, although many these methods have limited throughput. Rosenberg et al. describe a strategy called split-pool ligation-based transcriptome sequencing, or SPLiT-seq, which uses combinatorial barcoding transcriptomes without requiring physical isolation each cell. authors used their method >100,000 from brains and spinal cords 2 11 days after birth. Comparisons with situ hybridization data on RNA Allen Institute atlases linked spatial mapping, developmental lineages could be identified. Science , this issue p. 176

Language: Английский

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Alzheimer’s disease: A matter of blood–brain barrier dysfunction?

The Journal of Experimental Medicine, Journal Year: 2017, Volume and Issue: 214(11), P. 3151 - 3169

Published: Oct. 23, 2017

The blood-brain barrier (BBB) keeps neurotoxic plasma-derived components, cells, and pathogens out of the brain. An early BBB breakdown and/or dysfunction have been shown in Alzheimer's disease (AD) before dementia, neurodegeneration brain atrophy occur. However, role neurodegenerative disorders is still not fully understood. Here, we examine animal models frequently used to study pathophysiology AD, including transgenic mice expressing human amyloid-β precursor protein, presenilin 1, tau mutations, apolipoprotein E, strongest genetic risk factor for AD. We discuss process, pitfalls measurements, how targeting can influence course neurological disorder. Finally, comment on future approaches better define, at cellular molecular level, underlying mechanisms between as a basis developing new therapies repair control neurodegeneration.

Language: Английский

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Single-Cell Transcriptional Profiling Reveals Cellular Diversity and Intercommunication in the Mouse Heart

Cell Reports, Journal Year: 2018, Volume and Issue: 22(3), P. 600 - 610

Published: Jan. 1, 2018

Characterization of the cardiac cellulome, network cells that form heart, is essential for understanding development and normal organ function formulating precise therapeutic strategies to combat heart disease. Recent studies have reshaped our cellular composition highlighted important functional roles non-myocyte cell types. In this study, we characterized single-cell transcriptional profiles murine landscape using RNA sequencing (scRNA-seq). Detailed molecular analyses revealed diversity cellulome facilitated techniques isolate understudied populations, such as mural glia. Our also extensive networks intercellular communication suggested prevalent sexual dimorphism in gene expression heart. This study offers insights into structure mammalian provides an resource will stimulate biology.

Language: Английский

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Single-cell RNA sequencing of mouse brain and lung vascular and vessel-associated cell types

Scientific Data, Journal Year: 2018, Volume and Issue: 5(1)

Published: Aug. 21, 2018

Abstract Vascular diseases are major causes of death, yet our understanding the cellular constituents blood vessels, including how differences in their gene expression profiles create diversity vascular structure and function, is limited. In this paper, we describe a single-cell RNA sequencing (scRNA-seq) dataset that defines vessel-associated cell types subtypes mouse brain lung. The contains 3,436 single transcriptomes from brain, which formed 15 distinct clusters corresponding to (sub)types, another 1,504 lung, 17 clusters. order allow user-friendly access data, constructed searchable database ( http://betsholtzlab.org/VascularSingleCells/database.html ). Our constitutes comprehensive molecular atlas as such provides strong foundation for future studies development diseases.

Language: Английский

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Single-Cell Transcriptomics of a Human Kidney Allograft Biopsy Specimen Defines a Diverse Inflammatory Response

Journal of the American Society of Nephrology, Journal Year: 2018, Volume and Issue: 29(8), P. 2069 - 2080

Published: July 6, 2018

Background Single-cell genomics techniques are revolutionizing our ability to characterize complex tissues. By contrast, the used analyze renal biopsy specimens have changed little over several decades. We tested hypothesis that single-cell RNA-sequencing can comprehensively describe cell types and states in a human kidney specimen. Methods generated 8746 transcriptomes from healthy adult single transplant core by RNA-sequencing. Unsupervised clustering analysis of specimen was performed identify 16 distinct types, including all major immune most native this specimen, for which histologic read mixed rejection. Results Monocytes formed two subclusters representing nonclassical CD16+ group classic CD16− expressing dendritic maturation markers. The presence both monocyte subtypes validated staining independent specimens. Comparison epithelial with counterparts identified novel segment-specific proinflammatory responses Endothelial cells three subclusters: resting activated endothelial groups. One expressed Fc receptor pathway activation Ig internalization genes, consistent pathologic diagnosis antibody-mediated mapped previously defined genes associate rejection outcomes searchable online gene expression database. Conclusions present first step toward incorporation transcriptomics into interpretation, heterogeneous response rejection, provide resource scientific community.

Language: Английский

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Reducing Pericyte-Derived Scarring Promotes Recovery after Spinal Cord Injury

Cell, Journal Year: 2018, Volume and Issue: 173(1), P. 153 - 165.e22

Published: March 1, 2018

CNS injury often severs axons. Scar tissue that forms locally at the lesion site is thought to block axonal regeneration, resulting in permanent functional deficits. We report inhibiting generation of progeny by a subclass pericytes led decreased fibrosis and extracellular matrix deposition after spinal cord mice. Regeneration raphespinal corticospinal tract axons was enhanced sensorimotor function recovery improved following animals with attenuated pericyte-derived scarring. Using optogenetic stimulation, we demonstrate regenerated integrated into local circuitry below site. The number correlated recovery. In conclusion, attenuation represents promising therapeutic approach facilitate injury.

Language: Английский

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