scholarly journals A ligand motif enables differential vascular targeting of endothelial junctions between brain and retina

2019 ◽  
Vol 116 (6) ◽  
pp. 2300-2305 ◽  
Author(s):  
Fenny H. F. Tang ◽  
Fernanda I. Staquicini ◽  
André A. R. Teixeira ◽  
Jussara S. Michaloski ◽  
Gislene M. Namiyama ◽  
...  
Keyword(s):  
Binding Sites ◽  
Combinatorial Screening ◽  
Vascular Lumen ◽  
Transmission Electron ◽  
Endothelial Junctions ◽  
Endothelial Heterogeneity ◽  
Health And Disease ◽  
Preclinical And Clinical Studies ◽  
The Brain

Endothelial heterogeneity has important implications in health and disease. Molecular markers selectively expressed in the vasculature of different organs and tissues are currently being explored in targeted therapies with promising results in preclinical and clinical studies. Noteworthy is the role that combinatorial approaches such as phage display have had in identifying such markers by using phage as nanoparticles and surrogates for billions of different peptides, screening noninvasively the vascular lumen for binding sites. Here, we show that a new peptide motif that emerged from such combinatorial screening of the vasculature binds selectively to blood vessels in the brain in vivo but not to vessels in other organs. Peptides containing a conserved motif in which amino acids Phenylalanine−Arginine−Tryptophan (FRW) predominate could be visualized by transmission electron microscopy bound to the junctions between endothelial cells in all areas of the brain, including the optic nerve, but not in other barrier-containing tissues, such as intestines and testis. Remarkably, peptides containing the motif do not bind to vessels in the retina, implying an important molecular difference between these two vascular barriers. Furthermore, the peptide allows for in vivo imaging, demonstrating that new tools for studying and imaging the brain are likely to emerge from this motif.

Electromagnetic field in Alzheimer’s disease: a literature review of recent preclinical and clinical studies

2020 ◽  
Vol 17 ◽  
Author(s):  
Reem Habib Mohamad Ali Ahmad ◽  
Marc Fakhoury ◽  
Nada Lawand
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
In Vivo Studies ◽  
Key Factors ◽  
Potential Benefits ◽  
Preclinical And Clinical Studies ◽  
The Brain

: Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the progressive loss of neurons leading to cognitive and memory decay. The main signs of AD include the irregular extracellular accumulation of amyloidbeta (Aβ) protein in the brain and the hyper-phosphorylation of tau protein inside neurons. Changes in Aβ expression or aggregation are considered key factors in the pathophysiology of sporadic and early-onset AD and correlate with the cognitive decline seen in patients with AD. Despite decades of research, current approaches in the treatment of AD are only symptomatic in nature and are not effective in slowing or reversing the course of the disease. Encouragingly, recent evidence revealed that exposure to electromagnetic fields (EMF) can delay the development of AD and improve memory. This review paper discusses findings from in vitro and in vivo studies that investigate the link between EMF and AD at the cellular and behavioural level, and highlights the potential benefits of EMF as an innovative approach for the treatment of AD.

scholarly journals Microglia motility depends on neuronal activity and promotes structural plasticity in the hippocampus

2019 ◽  
Author(s):  
Felix C. Nebeling ◽  
Stefanie Poll ◽  
Lena C. Schmid ◽  
Manuel Mittag ◽  
Julia Steffen ◽  
...  
Keyword(s):  
Neuronal Activity ◽  
Dendritic Spines ◽  
Synapse Formation ◽  
Brain Parenchyma ◽  
Two Photon ◽  
Contact Rates ◽  
Health And Disease ◽  
The Impact ◽  
The Brain

AbstractMicroglia, the resident immune cells of the brain, play a complex role in health and disease. They actively survey the brain parenchyma by physically interacting with other cells and structurally shaping the brain. Yet, the mechanisms underlying microglia motility and their significance for synapse stability, especially during adulthood, remain widely unresolved. Here we investigated the impact of neuronal activity on microglia motility and its implication for synapse formation and survival. We used repetitive two-photon in vivo imaging in the hippocampus of awake mice to simultaneously study microglia motility and their interaction with synapses. We found that microglia process motility depended on neuronal activity. Simultaneously, more dendritic spines emerged in awake compared to anesthetized mice. Interestingly, microglia contact rates with individual dendritic spines were associated with their stability. These results suggest that microglia are not only sensing neuronal activity, but participate in synaptic rewiring of the hippocampus during adulthood, which has profound relevance for learning and memory processes.

scholarly journals Glucocorticoid receptor action in metabolic and neuronal function

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1208 ◽  
Author(s):  
Michael J. Garabedian ◽  
Charles A. Harris ◽  
Freddy Jeanneteau
Keyword(s):  
Gene Expression ◽  
Glucocorticoid Receptor ◽  
Metabolic Diseases ◽  
Cell Types ◽  
Health And Disease ◽  
And Behavior ◽  
External Signals ◽  
The Brain

Glucocorticoids via the glucocorticoid receptor (GR) have effects on a variety of cell types, eliciting important physiological responses via changes in gene expression and signaling. Although decades of research have illuminated the mechanism of how this important steroid receptor controls gene expression using in vitro and cell culture–based approaches, how GR responds to changes in external signals in vivo under normal and pathological conditions remains elusive. The goal of this review is to highlight recent work on GR action in fat cells and liver to affect metabolism in vivo and the role GR ligands and receptor phosphorylation play in calibrating signaling outputs by GR in the brain in health and disease. We also suggest that both the brain and fat tissue communicate to affect physiology and behavior and that understanding this “brain-fat axis” will enable a more complete understanding of metabolic diseases and inform new ways to target them.

scholarly journals Histology and Morphology of the Brain Subarachnoid Trabeculae

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Parisa Saboori ◽  
Ali Sadegh
Keyword(s):  
Animal Studies ◽  
Fibrous Tissue ◽  
Head Movements ◽  
Type I ◽  
Pia Mater ◽  
Transmission Electron ◽  
Bright Field Microscopy ◽  
The Brain

The interface between the brain and the skull consists of three fibrous tissue layers, dura mater, arachnoid, and pia mater, known as the meninges, and strands of collagen tissues connecting the arachnoid to the pia mater, known as trabeculae. The space between the arachnoid and the pia mater is filled with cerebrospinal fluid which stabilizes the shape and position of the brain during head movements or impacts. The histology and architecture of the subarachnoid space trabeculae in the brain are not well established in the literature. The only recognized fact about the trabeculae is that they are made of collagen fibers surrounded by fibroblast cells and they have pillar- and veil-like structures. In this work the histology and the architecture of the brain trabeculae were studied, via a series of in vivo and in vitro experiments using cadaveric and animal tissue. In the cadaveric study fluorescence and bright field microscopy were employed while scanning and transmission electron microscopy were used for the animal studies. The results of this study reveal that the trabeculae are collagen based type I, and their architecture is in the form of tree-shaped rods, pillars, and plates and, in some regions, they have a complex network morphology.

scholarly journals Isolation and in vitro culture of primary pia mater cells

2021 ◽  
Author(s):  
Fadi Saadeh ◽  
Jan Remsik ◽  
Camille Derderian ◽  
Yudan Chi ◽  
Adrienne Boire
Keyword(s):  
Brain Parenchyma ◽  
Pia Mater ◽  
Cell Functions ◽  
Flow Cytometric ◽  
Health And Disease ◽  
Unexplored Area ◽  
The Brain ◽  
Marker Identification

AbstractThe meninges remain an unexplored area of neurobiology. These structures play host to dozens of morbid pathologies. This protocol provides a reliable way to identify and isolate pial cells from mice using robust markers of pial identity in mouse and human tissues. We describe a protocol for the extraction of pia mater cells from mice and their culture as primary cells in vitro. Using an array of transcriptomic, histological, and flow cytometric analyses, we identified Icam1 and Slc38a2 as two novel pia mater markers in vitro and in vivo. Our results confirm the fibroblastoid nature of pial cells and their ability to form a sheet-like layer that covers the brain parenchyma. To our knowledge, this is the first published protocol for the isolation, tissue culture, and marker identification of pial cells from mice. These findings will enable researchers in CNS barriers to describe pial cell functions in both health and disease.

scholarly journals Imaging and Manipulating Pituitary Function in the Awake Mouse

Endocrinology ◽  
2019 ◽  
Vol 160 (10) ◽  
pp. 2271-2281 ◽  
Author(s):  
Ombeline Hoa ◽  
Chrystel Lafont ◽  
Pierre Fontanaud ◽  
Anne Guillou ◽  
Yasmine Kemkem ◽  
...  
Keyword(s):  
Pituitary Gland ◽  
Cell Types ◽  
Temporal Regulation ◽  
Hypothalamic Regulation ◽  
Health And Disease ◽  
Multiple Cell ◽  
Relationship Of ◽  
The Relationship ◽  
The Brain

Abstract Extensive efforts have been made to explore how the activities of multiple brain cells combine to alter physiology through imaging and cell-specific manipulation in different animal models. However, the temporal regulation of peripheral organs by the neuroendocrine factors released by the brain is poorly understood. We have established a suite of adaptable methodologies to interrogate in vivo the relationship of hypothalamic regulation with the secretory output of the pituitary gland, which has complex functional networks of multiple cell types intermingled with the vasculature. These allow imaging and optogenetic manipulation of cell activities in the pituitary gland in awake mouse models, in which both neuronal regulatory activity and hormonal output are preserved. These methodologies are now readily applicable for longitudinal studies of short-lived events (e.g., calcium signals controlling hormone exocytosis) and slowly evolving processes such as tissue remodeling in health and disease over a period of days to weeks.

scholarly journals Functional expression of SGLTs in rat brain

2010 ◽  
Vol 299 (6) ◽  
pp. C1277-C1284 ◽  
Author(s):  
Amy S. Yu ◽  
Bruce A. Hirayama ◽  
Gerald Timbol ◽  
Jie Liu ◽  
Ernest Basarah ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Brain Slices ◽  
Glucose Transporters ◽  
Functional Expression ◽  
Positron Emission ◽  
Health And Disease ◽  
Pass Through ◽  
The Brain

This work provides evidence of previously unrecognized uptake of glucose via sodium-coupled glucose transporters (SGLTs) in specific regions of the brain. The current understanding of functional glucose utilization in brain is largely based on studies using positron emission tomography (PET) with the glucose tracer 2-deoxy-2-[F-18]fluoro-d-glucose (2-FDG). However, 2-FDG is only a good substrate for facilitated-glucose transporters (GLUTs), not for SGLTs. Thus, glucose accumulation measured by 2-FDG omits the role of SGLTs. We designed and synthesized two high-affinity tracers: one, α-methyl-4-[F-18]fluoro-4-deoxy-d-glucopyranoside (Me-4FDG), is a highly specific SGLT substrate and not transported by GLUTs; the other one, 4-[F-18]fluoro-4-deoxy-d-glucose (4-FDG), is transported by both SGLTs and GLUTs and will pass through the blood brain barrier (BBB). In vitro Me-4FDG autoradiography was used to map the distribution of uptake by functional SGLTs in brain slices with a comparable result from in vitro 4-FDG autoradiography. Immunohistochemical assays showed that uptake was consistent with the distribution of SGLT protein. Ex vivo 4-FDG autoradiography showed that SGLTs in these areas are functionally active in the normal in vivo brain. The results establish that SGLTs are a normal part of the physiology of specific areas of the brain, including hippocampus, amygdala, hypothalamus, and cerebral cortices. 4-FDG PET imaging also established that this BBB-permeable SGLT tracer now offers a functional imaging approach in humans to assess regulation of SGLT activity in health and disease.

scholarly journals A luciferase prosubstrate and a red bioluminescent calcium indicator to image neuronal activity

2021 ◽  
Author(s):  
Xiaodong Tian ◽  
Yiyu Zhang ◽  
Xinyu Li ◽  
Ying Xiong ◽  
Tianchen Wu ◽  
...  
Keyword(s):  
Neuronal Activity ◽  
Nonspecific Esterase ◽  
New Paradigm ◽  
Fluorescent Indicators ◽  
Neuronal Ensembles ◽  
Brain Functions ◽  
Calcium Indicator ◽  
Health And Disease ◽  
The Brain

AbstractGenetically encoded fluorescent indicators have been broadly used to monitor neuronal activity in live animals, but invasive surgical procedures are required. This study presents a functional bioluminescence imaging (fBLI) method for recording the activity of neuronal ensembles in the brain in awake mice. We developed a luciferase prosubstrate activatable in vivo by nonspecific esterase to enhance the brain delivery of the luciferin. We further engineered a bright, bioluminescent indicator with robust responsiveness to calcium ions (Ca2+) and appreciable emission above 600 nm. Integration of these advantageous components enabled the imaging of Ca2+ dynamics in awake mice minimally invasively with excellent signal- to-background and subsecond temporal resolution. This study thus establishes a new paradigm for studying brain functions in health and disease.

scholarly journals Endothelial heterogeneity across distinct vascular beds during homeostasis and inflammation

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Ankit Jambusaria ◽  
Zhigang Hong ◽  
Lianghui Zhang ◽  
Shubhi Srivastava ◽  
Arundhati Jana ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Single Cell ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Cardiac Contractile ◽  
Organ Specific ◽  
Endothelial Heterogeneity ◽  
Vascular Beds ◽  
The Brain

Blood vessels are lined by endothelial cells engaged in distinct organ-specific functions but little is known about their characteristic gene expression profiles. RNA-Sequencing of the brain, lung, and heart endothelial translatome identified specific pathways, transporters and cell-surface markers expressed in the endothelium of each organ, which can be visualized at http://www.rehmanlab.org/ribo. We found that endothelial cells express genes typically found in the surrounding tissues such as synaptic vesicle genes in the brain endothelium and cardiac contractile genes in the heart endothelium. Complementary analysis of endothelial single cell RNA-Seq data identified the molecular signatures shared across the endothelial translatome and single cell transcriptomes. The tissue-specific heterogeneity of the endothelium is maintained during systemic in vivo inflammatory injury as evidenced by the distinct responses to inflammatory stimulation. Our study defines endothelial heterogeneity and plasticity and provides a molecular framework to understand organ-specific vascular disease mechanisms and therapeutic targeting of individual vascular beds.

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