Analysis of the brain mural cell transcriptome

Scientific Reports, Journal Year: 2016, Volume and Issue: 6(1)

Published: Oct. 11, 2016

Pericytes, the mural cells of blood microvessels, regulate microvascular development and function have been implicated in many brain diseases. However, due to a paucity defining markers, pericyte identification functional characterization remain ambiguous data interpretation problematic. In mice carrying two transgenic reporters, Pdgfrb-eGFP NG2-DsRed, we found that double-positive were vascular cells, while single reporters marked additional, but non-overlapping, neuroglial cells. Double-positive isolated by fluorescence-activated cell sorting (FACS) analyzed RNA sequencing. To reveal patterns transcripts, compared sequencing with from four previously published studies. The meta-analysis provided conservative catalogue 260 cell-enriched gene transcripts. We validated pericyte-specific expression novel vitronectin (Vtn) interferon-induced transmembrane protein 1 (Ifitm1), using fluorescent situ hybridization immunohistochemistry. further signaling pathways interaction networks pericyte-enriched genes silico. This work provides insight into molecular composition reported facilitates pericytes providing numerous new candidate marker is rich source for hypotheses future studies physiology pathophysiology.

Language: Английский

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Capillary pericytes express α-smooth muscle actin, which requires prevention of filamentous-actin depolymerization for detection

eLife, Journal Year: 2018, Volume and Issue: 7

Published: March 21, 2018

Recent evidence suggests that capillary pericytes are contractile and play a crucial role in the regulation of microcirculation. However, failure to detect components apparatus pericytes, most notably α-smooth muscle actin (α-SMA), has questioned these findings. Using strategies allow rapid filamentous-actin (F-actin) fixation (i.e. snap freeze with methanol at −20°C) or prevent F-actin depolymerization stabilizing agents), we demonstrate on mouse retinal capillaries, including those intermediate deeper plexus, express α-SMA. Junctional were more frequently α-SMA-positive relative linear segments. Intravitreal administration short interfering RNA (α-SMA-siRNA) suppressed α-SMA expression preferentially high order branch confirming existence smaller pool distal is quickly lost by depolymerization. We conclude do α-SMA, which rapidly depolymerizes during tissue thus evading detection immunolabeling.

Language: Английский

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Time to wake up: Studying neurovascular coupling and brain-wide circuit function in the un-anesthetized animal

NeuroImage, Journal Year: 2016, Volume and Issue: 153, P. 382 - 398

Published: Nov. 28, 2016

Functional magnetic resonance imaging (fMRI) has allowed the noninvasive study of task-based and resting-state brain dynamics in humans by inferring neural activity from blood-oxygenation-level dependent (BOLD) signal changes. An accurate interpretation hemodynamic changes that underlie fMRI signals depends on understanding quantitative relationship between cerebral blood flow, oxygenation volume. While there been extensive neurovascular coupling anesthetized animal models, anesthesia causes large disruptions metabolism, responsiveness cardiovascular function. Here, we review work showing circuit function awake are profoundly different those state. We argue time is right to bridge physiological mechanisms human neuroimaging signals, interpret them light underlying mechanisms. Lastly, discuss recent experimental innovations have enabled brain-wide un-anesthetized behaving models.

Language: Английский

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Targeting pericytes for therapeutic approaches to neurological disorders

Acta Neuropathologica, Journal Year: 2018, Volume and Issue: 136(4), P. 507 - 523

Published: Aug. 10, 2018

Many central nervous system diseases currently lack effective treatment and are often associated with defects in microvascular function, including a failure to match the energy supplied by blood used on neuronal computation, or breakdown of blood–brain barrier. Pericytes, an under-studied cell type located capillaries, crucial importance regulating diverse functions, such as angiogenesis, barrier, capillary flow movement immune cells into brain. They also form part "glial" scar isolating damaged parts CNS, may have stem cell-like properties. Recent studies suggested that pericytes play role neurological diseases, thus therapeutic target disorders stroke, traumatic brain injury, migraine, epilepsy, spinal cord diabetes, Huntington's disease, Alzheimer's multiple sclerosis, glioma, radiation necrosis amyotrophic lateral sclerosis. Here we report recent advances our understanding pericyte biology discuss how could be targeted develop novel approaches disorders, increasing flow, preserving barrier entry modulating formation vessels in, glial around, regions.

Language: Английский

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Markers for human brain pericytes and smooth muscle cells

Journal of Chemical Neuroanatomy, Journal Year: 2018, Volume and Issue: 92, P. 48 - 60

Published: June 7, 2018

Language: Английский

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Brain Microvascular Pericytes in Vascular Cognitive Impairment and Dementia

Frontiers in Aging Neuroscience, Journal Year: 2020, Volume and Issue: 12

Published: April 14, 2020

Pericytes are unique, multi-functional mural cells localized at the abluminal side of perivascular space in microvessels. Originally discovered nineteenth century, pericytes had drawn less attention until decades ago mainly due to lack specific markers. Recently, however, a growing body evidence has revealed that play various important roles: development and maintenance blood-brain barrier (BBB), regulation neurovascular system (e.g., vascular stability, vessel formation, cerebral blood flow, etc.), trafficking inflammatory cells, clearance toxic waste products from brain, acquisition stem cell-like properties. In unit, perform these functions through coordinated crosstalk with neighboring including endothelial, glial, neuronal cells. Dysfunction contribute wide variety diseases lead cognitive impairments such as small disease (SVD), acute stroke, Alzheimer’s (AD), other neurological disorders. For instance, SVDs, pericyte degeneration leads microvessel instability demyelination while constriction after ischemia causes no-reflow phenomenon brain capillaries. AD, which shares some common risk factors dementia, reduction coverage subsequent microvascular observed association white matter attenuation impaired cognition. Pericyte loss BBB-breakdown, stagnates amyloid β leakage neurotoxic molecules into parenchyma. this review, we first summarize characteristics pericytes, their roles central nervous system. Then, focus on how dysfunctional pathogenesis impairment ‘small vessel’ ‘large diseases, well AD. Finally, discuss therapeutic implications for disorders by targeting pericytes.

Language: Английский

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Dynamic Remodeling of Pericytes In Vivo Maintains Capillary Coverage in the Adult Mouse Brain

Cell Reports, Journal Year: 2018, Volume and Issue: 22(1), P. 8 - 16

Published: Jan. 1, 2018

Highlights•Brain capillary pericytes negotiate vascular territories with adjacent pericytes•Pericytes can extend or retract their processes on the timescale of days•Ablation a pericyte evokes robust extension from pericytes•Loss contact leads to local dilation until is regainedSummaryDirect and communication between endothelial cells critical for maintenance cerebrovascular stability blood-brain barrier function. Capillary have thin that reach hundreds micrometers along bed. The come in close proximity but do not overlap, yielding cellular chain discrete occupied by individual pericytes. Little known about whether this structurally dynamic adult brain. Using vivo two-photon imaging mouse cortex, we show while somata were immobile, tips underwent extensions and/or retractions over days. selective ablation single provoked exuberant neighboring uncovered regions endothelium. Uncovered had normal function dilated was regained. Pericyte structural plasticity may be health warrants detailed investigation.Graphical abstract

Language: Английский

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Linking brain vascular physiology to hemodynamic response in ultra-high field MRI

NeuroImage, Journal Year: 2017, Volume and Issue: 168, P. 279 - 295

Published: Feb. 23, 2017

Functional MRI using blood oxygenation level-dependent (BOLD) contrast indirectly probes neuronal activity via evoked cerebral volume (CBV) and changes. Thus, its spatio-temporal characteristics are determined by vascular physiology parameters. In this paper, we focus on the spatial distribution time course of fMRI signal their magnetic field strength dependence. Even though much is still unknown, following consistent picture emerging: a) For high resolution imaging, contrast-to-noise increases supra-linearly with strength. b) The location spacing penetrating arteries ascending veins in cortical tissue not correlated to columns, imposing limitations achievable point-spread function (PSF) fMRI. c) Baseline CBV may vary over layers biasing values. d) largest change microvasculature, less surface even pial veins. e) Venous changes only relevant for longer stimuli, post-capillary vessels. f) balloon effect (i.e. slow recovery baseline) located tissue, fact that post-stimulus undershoot has narrower PSF than positive BOLD response. g) onset stimulation been found be shortest middle/lower layers, both optical imaging high-resolution fMRI, but argue demonstrate simulations varying latencies can also caused properties and, therefore, potentially interpreted as neural latencies. With simulations, illustrate dependency transients, such adaptation during stimulation, initial dip undershoot. sum, structure impose give rise complex which contain time-varying amount excitatory inhibitory information. Nevertheless, non-invasive at ultra-high fields provides an unprecedented detailed view cognitive processes human brain.

Language: Английский

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Contractile pericytes determine the direction of blood flow at capillary junctions

Proceedings of the National Academy of Sciences, Journal Year: 2020, Volume and Issue: 117(43), P. 27022 - 27033

Published: Oct. 13, 2020

The essential function of the circulatory system is to continuously and efficiently supply O2 nutrients necessary meet metabolic demands every cell in body, a which vast capillary networks play key role. Capillary serve an additional important central nervous system: acting as sensory network, they detect neuronal activity form elevated extracellular K+ initiate retrograde, propagating, hyperpolarizing signal that dilates upstream arterioles rapidly increase local blood flow. Yet, little known about how entering this network distributed on branch-to-branch basis reach specific neurons need. Here, we demonstrate capillary-enwrapping projections junctional, contractile pericytes within postarteriole transitional region differentially constrict structurally dynamically determine morphology junctions thereby regulate branch-specific We further found these are capable receiving propagating K+-induced signals through channeling red cells toward initiating signal. By controlling flow at junctions, functionally distinct maintain efficiency effectiveness enabling optimal perfusion brain.

Language: Английский

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CD146 coordinates brain endothelial cell–pericyte communication for blood–brain barrier development

Proceedings of the National Academy of Sciences, Journal Year: 2017, Volume and Issue: 114(36)

Published: Aug. 21, 2017

Significance Development of the blood–brain barrier (BBB) requires spatiotemporal coordination cerebrovascular endothelial cells (ECs) and pericytes. Until now, molecular mechanism(s) coordinating pericyte–EC behaviors during this process have been incompletely understood. In study, combining analysis EC-/pericyte-specific Cd146 -KO mice in vitro BBB models, we report CD146 as a dynamic coordinator regulating communication between ECs pericytes within neurovascular unit development. Our study demonstrates that single cell-adhesion receptor, CD146, acts an essential regulator to coordinate formation embryogenesis. Furthermore, it identifies potential key therapeutic target for neurological diseases related disorders.

Language: Английский

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