An original infection model identifies host lipoprotein import as a route for blood-brain barrier crossing DOI Creative Commons
Billel Benmimoun, Florentia Papastefanaki, Bruno Périchon

et al.

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: Nov. 30, 2020

Abstract Pathogens able to cross the blood-brain barrier (BBB) induce long-term neurological sequelae and death. Understanding how neurotropic pathogens bypass this strong physiological is a prerequisite devise therapeutic strategies. Here we propose an innovative model of infection in developing Drosophila brain, combining whole brain explants with vivo systemic infection. We find that several mammalian are BBB, including Group B Streptococcus (GBS). Amongst GBS surface components, lipoproteins, particular leucine-rich Blr, important for BBB crossing virulence . Further, identify (V)LDL receptor LpR2, expressed as host allowing translocation through endocytosis. Finally, show Blr required pathogenicity murine Our results demonstrate potential studying by new mechanism which exploit machinery barriers generate

Language: Английский

The glia of the adult Drosophila nervous system DOI Creative Commons

Malte C. Kremer,

Christophe Jung,

Sara Batelli

et al.

Glia, Journal Year: 2017, Volume and Issue: 65(4), P. 606 - 638

Published: Jan. 30, 2017

Glia play crucial roles in the development and homeostasis of nervous system. While GLIA Drosophila embryo have been well characterized, their study adult system has limited. Here, we present a detailed description glia system, based on analysis some 500 glial drivers identified within collection synthetic GAL4 lines. We find that make up ∼10% cells envelop all compartments neurons (soma, dendrites, axons) as whole. Our morphological suggests set simple rules governing morphogenesis interactions with other cells. All subtypes minimize contact neighbors but maximize adapt macromorphology micromorphology to neuronal entities they envelop. Finally, show no obvious spatial organization or registration entities. regional specializations, together powerful genetic toolkit provide, will facilitate functional mature 2017 2017;65:606–638

Language: Английский

Citations

261

Regulation of the Blood–Brain Barrier by Circadian Rhythms and Sleep DOI Creative Commons
Vishnu Anand Cuddapah, Shirley Zhang, Amita Sehgal

et al.

Trends in Neurosciences, Journal Year: 2019, Volume and Issue: 42(7), P. 500 - 510

Published: June 25, 2019

Language: Английский

Citations

156

Transcriptional complexity in the insect central complex: single nuclei RNA-sequencing of adult brain neurons derived from type 2 neuroblasts DOI Open Access
Derek Epiney, Gonzalo N Morales Chaya, Noah Dillon

et al.

Published: Feb. 27, 2025

In both invertebrates such as Drosophila and vertebrates mouse or human, the brain contains most diverse population of cell types any tissue. It is generally accepted that transcriptional diversity an early step in generating neuronal glial diversity, followed by establishment a unique gene expression profile determines morphology, connectivity, function. , there are two neural stem cells, called Type 1 (T1) 2 (T2) neuroblasts. contrast to T1 neuroblasts, T2 neuroblasts generate intermediate progenitors (INPs) expand number types. The T2-derived neurons contributes large portion central complex (CX), conserved region plays role sensorimotor integration. Recent work has revealed much connectome CX, but how this assembled remains unclear. Mapping derived from necessary linking assembly adult brain. Here we perform single nuclei RNA sequencing neuroblast-derived glia. We identify clusters containing all known classes glia, male/female enriched, 161 neuron-specific clusters. map neurotransmitter neuropeptide transcription factor combinatorial codes for each cluster (presumptive neuron subtype). This directs functional studies determine whether code specifies distinct type within CX. several columnar subtypes (NPF+ AstA+) closely related Our data support hypothesis represents one few subtypes.

Language: Английский

Citations

2

Plant Defense Against Herbivory and Insect Adaptations DOI Creative Commons
Abdul Rashid War, Gaurav Kumar Taggar, Barkat Hussain

et al.

AoB Plants, Journal Year: 2018, Volume and Issue: unknown

Published: June 11, 2018

There is always a silent war between plants and herbivorous insects that we are rarely privy to. In this war, chemicals act as both weapons messengers. Insect–plant co-evolution going on for millions of years. Plants look new strategies to avoid insect pests insects, in turn, ready develop counter-adaptations. This intricate interaction has led the development number plant defensive traits counter-adaptive features well. Both have developed morphological biochemical dodge each other’s strategies. However, interactions considered more important effective than ones because their dynamic nature. Some evolved during evolution include toxic furanocoumarins, amino acids, trichomes, lignin latex. Since there an increasing focus improving crop production through safe sustainable means by reducing reliance pesticides, it highly understand against herbivory. It equally adaptations these order deploy management outsmart pests. Here discuss defence herbivory, induction elicitors and/or damage, counter-adaptation

Language: Английский

Citations

135

The biological significance of brain barrier mechanisms: help or hindrance in drug delivery to the central nervous system? DOI Creative Commons
Norman R. Saunders, Mark D. Habgood, Kjeld Møllgård

et al.

F1000Research, Journal Year: 2016, Volume and Issue: 5, P. 313 - 313

Published: March 10, 2016

Barrier mechanisms in the brain are important for its normal functioning and development. Stability of brain's internal environment, particularly with respect to ionic composition, is a prerequisite fundamental basis function, namely transmission nerve impulses. In addition, appropriate controlled supply wide range nutrients such as glucose, amino acids, monocarboxylates, vitamins also essential development function. These all cellular functions across interfaces that separate from rest environment body. An morphological component but one barriers presence specialized intercellular tight junctions between cells comprising interface: endothelial blood-brain barrier itself, arachnoid membrane, choroid plexus epithelial cells, tanycytes (specialized glial cells) circumventricular organs. ependyma lining cerebral ventricles adult brain, joined by gap junctions, which not restrictive movement molecules. But developing forerunners these form neuroepithelium, restricts exchange smallest molecules cerebrospinal fluid interstitial because strap cells. The physical their properties. proper, this combined paucity vesicular transport characteristic other vascular beds. Without diffusional restrain, would be ineffective. Superimposed on structures physiological contain various metabolic transporters efflux pumps, often ATP-binding cassette (ABC) transporters, provide an either preventing entry or expelling numerous including toxins, drugs, xenobiotics. review, we summarize influx well indicating likely involvement neuropathologies. There have been extensive attempts overcome prevent many drugs therapeutic potential into brain. We outline those tried discuss why they may so far largely unsuccessful. Currently, promising approach appears focal, reversible disruption using focused ultrasound, more work required evaluate method before it can patients. Overall, our view much knowledge new experimental methods will drug targeting successful endeavor. studies, if applied pathologies stroke, trauma, multiple sclerosis, aid defining contribution pathology conditions, causative secondary.

Language: Английский

Citations

128

Blood–brain barrier alterations and their impact on Parkinson’s disease pathogenesis and therapy DOI Creative Commons

Kristina Lau,

Rebecca Kotzur,

Franziska Richter

et al.

Translational Neurodegeneration, Journal Year: 2024, Volume and Issue: 13(1)

Published: July 29, 2024

There is increasing evidence for blood-brain barrier (BBB) alterations in Parkinson's disease (PD), the second most common neurodegenerative disorder with rapidly rising prevalence. Altered tight junction and transporter protein levels, accumulation of α-synuclein increase inflammatory processes lead to extravasation blood molecules vessel degeneration. This could result a self-perpetuating pathophysiology inflammation BBB alteration, which contribute neurodegeneration. Toxin exposure or over-expression animal models has been shown initiate similar pathologies, providing platform study underlying mechanisms therapeutic interventions. Here we provide comprehensive review current knowledge on PD patients how rodent that replicate some these changes can be used mechanisms. Specific challenges assessing healthy controls are discussed. Finally, potential role pathogenesis possible implications therapy explored. The interference novel strategies requires more attention. Brain region-specific also open up opportunities target specifically vulnerable neuronal subpopulations.

Language: Английский

Citations

14

Microphysiological Blood‐Brain Barrier Systems for Disease Modeling and Drug Development DOI

Atharva R. Mulay,

Ji‐Hyun Hwang, Deok‐Ho Kim

et al.

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: 13(21)

Published: March 2, 2024

Abstract The blood‐brain barrier (BBB) is a highly controlled microenvironment that regulates the interactions between cerebral blood and brain tissue. Due to its selectivity, many therapeutics targeting various neurological disorders are not able penetrate into Pre‐clinical studies using animals other in vitro platforms have shown ability fully replicate human BBB leading failure of majority clinical trials. However, recent innovations ex vivo modeling called organs‐on‐chips potential create more accurate disease models for improved drug development. These microfluidic induce physiological stressors on cultured cells generate physiologically BBBs compared previous models. In this review, different approaches BBBs‐on‐chips explored alongside their application therapeutic efficacy. Additionally, use delivery discussed, advances linking onto multiorgan mimic organ crosstalk reviewed.

Language: Английский

Citations

10

Blood‐brain barrier development: Systems modeling and predictive toxicology DOI
Katerine S. Saili, Todd J. Zurlinden, Andrew J. Schwab

et al.

Birth Defects Research, Journal Year: 2017, Volume and Issue: 109(20), P. 1680 - 1710

Published: Dec. 1, 2017

The blood-brain barrier (BBB) serves as a gateway for passage of drugs, chemicals, nutrients, metabolites, and hormones between vascular neural compartments in the brain. Here, we review BBB development with regard to microphysiology neurovascular unit (NVU) impact disruption on brain development. Our focus is modeling these complex systems. Extant silico models are available tools predict probability drug/chemical across BBB; vitro platforms high-throughput screening high-content imaging provide novel data streams profiling chemical-biological interactions; engineered human cell-based microphysiological systems empirical which investigate dynamics NVU function. Computational needed that bring together kinetic dynamic aspects function gestation under various physiological toxicological scenarios. This integration will inform adverse outcome pathways reduce uncertainty translating use risk assessments aim protect neurodevelopmental health.

Language: Английский

Citations

78

The gut reaction to traumatic brain injury DOI Open Access

Rebeccah J. Katzenberger,

Barry Ganetzky, David A. Wassarman

et al.

Fly, Journal Year: 2015, Volume and Issue: 9(2), P. 68 - 74

Published: April 3, 2015

Traumatic brain injury (TBI) is a complex disorder that affects millions of people worldwide. The complexity TBI partly stems from the fact injuries to instigate non-neurological other organs such as intestine. Additionally, genetic variation thought play large role in determining nature and severity injuries. We recently reported flies, humans, increases permeability intestinal epithelial barrier resulting hyperglycemia higher risk death. Furthermore, we demonstrated flies also pertinent following TBI. goals this review are place our findings context what known about TBI-induced studies patients rodent models draw attention how fly model can provide unique insights may facilitate diagnosis treatment

Language: Английский

Citations

67

Tumor-induced disruption of the blood-brain barrier promotes host death DOI Creative Commons
Jung Kim,

Hsiu‐Chun Chuang,

Natalie K. Wolf

et al.

Developmental Cell, Journal Year: 2021, Volume and Issue: 56(19), P. 2712 - 2721.e4

Published: Sept. 7, 2021

Language: Английский

Citations

50