Rearranging the coupling architecture in the brain in response to the introduction of various endocannabinoid receptor ligands

2020 ◽  
Author(s):  
Marina V. Sysoeva
Keyword(s):  
Receptor Ligands ◽  
Endocannabinoid Receptor ◽  
The Brain

scholarly journals Innate Immune Regulation by Toll-Like Receptors in the Brain

2012 ◽  
Vol 2012 ◽  
pp. 1-19 ◽  
Author(s):  
Carina Mallard
Keyword(s):  
Immune Regulation ◽  
Innate Immune System ◽  
Innate Immune ◽  
Toll Like Receptor ◽  
Toll Like Receptors ◽  
Receptor Ligands ◽  
Health And Disease ◽  
Cerebral Inflammation ◽  
The Brain

The innate immune system plays an important role in cerebral health and disease. In recent years the role of innate immune regulation by toll-like receptors in the brain has been highlighted. In this paper the expression of toll-like receptors and endogenous toll-like receptor ligands in the brain and their role in cerebral ischemia will be discussed. Further, the ability of systemic toll-like receptor ligands to induce cerebral inflammation will be reviewed. Finally, the capacity of toll-like receptors to both increase (sensitization) and decrease (preconditioning/tolerance) the vulnerability of the brain to damage will be disclosed. Studies investigating the role of toll-like receptors in the developing brain will be emphasized.

scholarly journals Intracellular uptake of macromolecules by brain lymphatic endothelial cells during zebrafish embryonic development

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Max van Lessen ◽  
Shannon Shibata-Germanos ◽  
Andreas van Impel ◽  
Thomas A Hawkins ◽  
Jason Rihel ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Mannose Receptor ◽  
Adult Brain ◽  
Molecular Signature ◽  
Lymphatic Endothelial Cells ◽  
Tubular Structures ◽  
Receptor Ligands ◽  
Uptake Mechanism ◽  
Vertebrate Embryo ◽  
The Brain

The lymphatic system controls fluid homeostasis and the clearance of macromolecules from interstitial compartments. In mammals brain lymphatics were only recently discovered, with significant implications for physiology and disease. We examined zebrafish for the presence of brain lymphatics and found loosely connected endothelial cells with lymphatic molecular signature covering parts of the brain without forming endothelial tubular structures. These brain lymphatic endothelial cells (BLECs) derive from venous endothelium, are distinct from macrophages, and are sensitive to loss of Vegfc. BLECs endocytose macromolecules in a selective manner, which can be blocked by injection of mannose receptor ligands. This first report on brain lymphatic endothelial cells in a vertebrate embryo identifies cells with unique features, including the uptake of macromolecules at a single cell level. Future studies will address whether this represents an uptake mechanism that is conserved in mammals and how these cells affect functions of the embryonic and adult brain.

scholarly journals Dynamic changes to the endocannabinoid system in models of chronic pain

2012 ◽  
Vol 367 (1607) ◽  
pp. 3300-3311 ◽  
Author(s):  
Devi Rani Sagar ◽  
James J. Burston ◽  
Stephen G. Woodhams ◽  
Victoria Chapman
Keyword(s):  
Chronic Pain ◽  
Endocannabinoid System ◽  
Receptor Expression ◽  
Biologically Active ◽  
Receptor Ligands ◽  
Receptor System ◽  
Analgesic Effects ◽  
Endocannabinoid Receptor ◽  
The Impact ◽  
Local Levels

The analgesic effects of cannabinoid ligands, mediated by CB1 receptors are well established. However, the side-effect profile of CB1 receptor ligands has necessitated the search for alternative cannabinoid-based approaches to analgesia. Herein, we review the current literature describing the impact of chronic pain states on the key components of the endocannabinoid receptor system, in terms of regionally restricted changes in receptor expression and levels of key metabolic enzymes that influence the local levels of the endocannabinoids. The evidence that spinal CB2 receptors have a novel role in the modulation of nociceptive processing in models of neuropathic pain, as well as in models of cancer pain and arthritis is discussed. Recent advances in our understanding of the spinal location of the key enzymes that regulate the levels of the endocannabinoid 2-AG are discussed alongside the outcomes of recent studies of the effects of inhibiting the catabolism of 2-AG in models of pain. The complexities of the enzymes capable of metabolizing both anandamide (AEA) and 2-AG have become increasingly apparent. More recently, it has come to light that some of the metabolites of AEA and 2-AG generated by cyclooxygenase-2, lipoxygenases and cytochrome P450 are biologically active and can either exacerbate or inhibit nociceptive signalling.

scholarly journals Trapping of Nicotinic Acetylcholine Receptor Ligands Assayed by in vitro Cellular Studies and in vivo PET Imaging

2021 ◽  
Author(s):  
Hannah Zhang ◽  
Chien-Min Kao ◽  
Matthew Zammit ◽  
Anitha P Govind ◽  
Samuel Mitchell ◽  
...  
Keyword(s):  
Residence Time ◽  
Pet Imaging ◽  
Nicotinic Receptors ◽  
Receptor Ligands ◽  
Ph Gradients ◽  
High Affinity ◽  
Acidic Vesicles ◽  
The Brain

A question relevant to nicotine addiction is how nicotine and other nicotinic receptor membrane-permeant ligands, such as the anti-smoking drug varenicline (Chantix), distribute in the brain. Previously, we found that varenicline is trapped in intracellular acidic vesicles that contain α4β2-type nicotinic receptors (α4β2Rs). Nicotine is not trapped but concentrates there. Here, combining subcellular methods with in vivo PET imaging, we present evidence that the α4β2R PET ligand, 2-FA85380 (2-FA), is trapped within α4β2R-containing acidic vesicles, while the PET ligand, Nifene, is not trapped. Additional evidence, using a fluorescent-tagged α4β2R PET ligand, Nifrolidine, identified the trapping vesicles as Golgi satellites, an organelle regulated by nicotine in neurons where α4β2Rs are expressed and traffics and processes α4β2Rs in those neurons. Using PET imaging, 2-[18F]FA kinetics in high α4β2R-expressing regions were much slower than ligand unbinding rates consistent with 2-FA trapping in Golgi satellites extending ligand residence time and 2-[18F]FA imaging of the Golgi satellites. Chloroquine, which dissipates acidic organelle pH gradients, reduced 2-[18F]FA distribution in vivo consistent with ligand trapping. In contrast, [18F]Nifene kinetics were rapid, consistent with ligand residence time reflecting ligand unbinding rates, and [18F]Nifene imaging all α4β2R pools. Specific 2-[18F]FA and [18F]Nifene signals were eliminated in β2 subunit knockout mice or by acute nicotine injections demonstrating binding to high-affinity sites on β2-containing receptors. Altogether, we find that kinetic differences in α4β2R PET ligands are consistent with their distribution among different α4β2R pools in the brain, [18F]Nifene binding and imaging all ligand-binding α4β2Rs and 2-[18F]FA imaging α4β2Rs in Golgi satellites.

Clinical applications of single photon emission tomography in neuromedicine

2000 ◽  
Vol 39 (07) ◽  
pp. 180-195 ◽  
Author(s):  
F. Grünwald ◽  
T. Kuwert ◽  
K. Tatsch ◽  
O. Sabri ◽  
O. Benkert ◽  
...  
Keyword(s):  
Single Photon ◽  
Imaging Modality ◽  
Photon Emission ◽  
Clinical Applications ◽  
Single Photon Emission Tomography ◽  
Emission Tomography ◽  
Receptor Ligands ◽  
Single Photon Emission ◽  
The Brain ◽  
Photon Emission Tomography

SummarySingle photon emission tomography is, because of its availability and the relatively low costs, the functional imaging modality currently most widely used for clinical applications in the brain. Beside the application of radiopharmaceuticals for the assessment of regional cerebral blood flow there is an increasing clinical use of more selective SPECT-radiopharmaceuticals, like amino acid analogs or receptor ligands. This article gives in his first part a critical review of the clinical applications of SPECT in neuro-oncology, epilepsy, basal ganglia disorders and cerebrovascular disease.

scholarly journals Correlations between the Memory-Related Behavior and the Level of Oxidative Stress Biomarkers in the Mice Brain, Provoked by an Acute Administration of CB Receptor Ligands

2016 ◽  
Vol 2016 ◽  
pp. 1-15 ◽  
Author(s):  
Marta Kruk-Slomka ◽  
Anna Boguszewska-Czubara ◽  
Tomasz Slomka ◽  
Barbara Budzynska ◽  
Grazyna Biala
Keyword(s):  
Oxidative Stress ◽  
Long Term Memory ◽  
Acute Administration ◽  
Cb2 Receptor ◽  
Receptor Ligands ◽  
Oxidative Stress Biomarkers ◽  
Stress Biomarkers ◽  
Mice Brain ◽  
The Brain

The endocannabinoid system, through cannabinoid (CB) receptors, is involved in memory-related responses, as well as in processes that may affect cognition, like oxidative stress processes. The purpose of the experiments was to investigate the impact of CB1 and CB2 receptor ligands on the long-term memory stages in male Swiss mice, using the passive avoidance (PA) test, as well as the influence of these compounds on the level of oxidative stress biomarkers in the mice brain. A single injection of a selective CB1 receptor antagonist, AM 251, improved long-term memory acquisition and consolidation in the PA test in mice, while a mixed CB1/CB2 receptor agonist WIN 55,212-2 impaired both stages of cognition. Additionally, JWH 133, a selective CB2 receptor agonist, and AM 630, a competitive CB2 receptor antagonist, significantly improved memory. Additionally, an acute administration of the highest used doses of JWH 133, WIN 55,212-2, and AM 630, but not AM 251, increased total antioxidant capacity (TAC) in the brain. In turn, the processes of lipids peroxidation, expressed as the concentration of malondialdehyde (MDA), were more advanced in case of AM 251. Thus, some changes in the PA performance may be connected with the level of oxidative stress in the brain.

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