scholarly journals The Roles of Lpar1 in Central Nervous System Disorders and Diseases

2021 ◽  
Vol 15 ◽  
Author(s):  
Dongqiong Xiao ◽  
Xiaojuan Su ◽  
Hu Gao ◽  
Xihong Li ◽  
Yi Qu
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cell Types ◽  
Potential Therapeutic Target ◽  
Cns Disorders ◽  
The Central Nervous System ◽  
Almost All ◽  
G Protein Coupled ◽  
Differentiation Gene ◽  
The Brain

Lysophosphatidic acid receptor 1 (Lpar1), which is found in almost all human tissues but is most abundant in the brain, can couple to G protein-coupled receptors (GPCRs) and participate in regulating cell proliferation, migration, survival, and apoptosis. Endothelial differentiation gene-2 receptor (Edg2), the protein encoded by the Lpar1 gene, is present on various cell types in the central nervous system (CNS), such as neural stem cells (NSCs), oligodendrocytes, neurons, astrocytes, and microglia. Lpar1 deletion causes neurodevelopmental disorders and CNS diseases, such as brain cancer, neuropsychiatric disorders, demyelination diseases, and neuropathic pain. Here, we summarize the possible roles and mechanisms of Lpar1/Edg2 in CNS disorders and diseases and propose that Lpar1/Edg2 might be a potential therapeutic target for CNS disorders and diseases.

scholarly journals Purinergic Receptors of the Central Nervous System: Biology, PET Ligands, and Their Applications

2020 ◽  
Vol 19 ◽  
pp. 153601212092760
Author(s):  
Hamideh Zarrinmayeh ◽  
Paul R. Territo
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Purinergic Receptors ◽  
P2y Receptors ◽  
Cns Disorders ◽  
Extracellular Adenosine ◽  
Functional Roles ◽  
Positron Emission ◽  
The Central Nervous System ◽  
The Brain

Purinergic receptors play important roles in central nervous system (CNS). These receptors are involved in cellular neuroinflammatory responses that regulate functions of neurons, microglial and astrocytes. Based on their endogenous ligands, purinergic receptors are classified into P1 or adenosine, P2X and P2Y receptors. During brain injury or under pathological conditions, rapid diffusion of extracellular adenosine triphosphate (ATP) or uridine triphosphate (UTP) from the damaged cells, promote microglial activation that result in the changes in expression of several of these receptors in the brain. Imaging of the purinergic receptors with selective Positron Emission Tomography (PET) radioligands has advanced our understanding of the functional roles of some of these receptors in healthy and diseased brains. In this review, we have accumulated a list of currently available PET radioligands of the purinergic receptors that are used to elucidate the receptor functions and participations in CNS disorders. We have also reviewed receptors lacking radiotracer, laying the foundation for future discoveries of novel PET radioligands to reveal these receptors roles in CNS disorders.

scholarly journals On the role of the extracellular space on the holistic behavior of the brain

2015 ◽  
Vol 26 (5) ◽  
pp. 489-506 ◽  
Author(s):  
Manuela Marcoli ◽  
Luigi F. Agnati ◽  
Francesco Benedetti ◽  
Susanna Genedani ◽  
Diego Guidolin ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Extracellular Matrix ◽  
Nervous System ◽  
Cellular Networks ◽  
Intercellular Communication ◽  
Extracellular Space ◽  
Cell Types ◽  
Molecular Network ◽  
The Central Nervous System ◽  
The Brain

AbstractMultiple players are involved in the brain integrative action besides the classical neuronal and astrocyte networks. In the past, the concept of complex cellular networks has been introduced to indicate that all the cell types in the brain can play roles in its integrative action. Intercellular communication in the complex cellular networks depends not only on well-delimited communication channels (wiring transmission) but also on diffusion of signals in physically poorly delimited extracellular space pathways (volume transmission). Thus, the extracellular space and the extracellular matrix are the main players in the intercellular communication modes in the brain. Hence, the extracellular matrix is an ‘intelligent glue’ that fills the brain and, together with the extracellular space, contributes to the building-up of the complex cellular networks. In addition, the extracellular matrix is part of what has been defined as the global molecular network enmeshing the entire central nervous system, and plays important roles in synaptic contact homeostasis and plasticity. From these premises, a concept is introduced that the global molecular network, by enmeshing the central nervous system, contributes to the brain holistic behavior. Furthermore, it is suggested that plastic ‘brain compartments’ can be detected in the central nervous system based on the astrocyte three-dimensional tiling of the brain volume and on the existence of local differences in cell types and extracellular space fluid and extracellular matrix composition. The relevance of the present view for neuropsychiatry is discussed. A glossary box with terms and definitions is provided.

scholarly journals Cerebral Apolipoprotein D Exits the Brain and Accumulates in Peripheral Tissues

2021 ◽  
Vol 22 (8) ◽  
pp. 4118
Author(s):  
Frederik Desmarais ◽  
Vincent Hervé ◽  
Karl F. Bergeron ◽  
Gaétan Ravaut ◽  
Morgane Perrotte ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cell Types ◽  
Strongly Correlated ◽  
Peripheral Tissues ◽  
Additional Cell ◽  
The Central Nervous System ◽  
Apolipoprotein D ◽  
Pass Through ◽  
The Brain

Apolipoprotein D (ApoD) is a secreted lipocalin associated with neuroprotection and lipid metabolism. In rodent, the bulk of its expression occurs in the central nervous system. Despite this, ApoD has profound effects in peripheral tissues, indicating that neural ApoD may reach peripheral organs. We endeavor to determine if cerebral ApoD can reach the circulation and accumulate in peripheral tissues. Three hours was necessary for over 40% of all the radiolabeled human ApoD (hApoD), injected bilaterally, to exit the central nervous system (CNS). Once in circulation, hApoD accumulates mostly in the kidneys/urine, liver, and muscles. Accumulation specificity of hApoD in these tissues was strongly correlated with the expression of lowly glycosylated basigin (BSG, CD147). hApoD was observed to pass through bEnd.3 blood brain barrier endothelial cells monolayers. However, cyclophilin A did not impact hApoD internalization rates in bEnd.3, indicating that ApoD exit from the brain is either independent of BSG or relies on additional cell types. Overall, our data showed that ApoD can quickly and efficiently exit the CNS and reach the liver and kidneys/urine, organs linked to the recycling and excretion of lipids and toxins. This indicated that cerebral overexpression during neurodegenerative episodes may serve to evacuate neurotoxic ApoD ligands from the CNS.

scholarly journals Plectin in the Central Nervous System and a Putative Role in Brain Astrocytes

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2353
Author(s):  
Maja Potokar ◽  
Jernej Jorgačevski
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Current Knowledge ◽  
Cell Types ◽  
Cellular Proteins ◽  
Bidirectional Communication ◽  
The Central Nervous System ◽  
Brain And Spinal Cord ◽  
The Brain

Plectin, a high-molecular-mass cytolinker, is abundantly expressed in the central nervous system (CNS). Currently, a limited amount of data about plectin in the CNS prevents us from seeing the complete picture of how plectin affects the functioning of the CNS as a whole. Yet, by analogy to its role in other tissues, it is anticipated that, in the CNS, plectin also functions as the key cytoskeleton interlinking molecule. Thus, it is likely involved in signalling processes, thereby affecting numerous fundamental functions in the brain and spinal cord. Versatile direct and indirect interactions of plectin with cytoskeletal filaments and enzymes in the cells of the CNS in normal physiological and in pathologic conditions remain to be fully addressed. Several pathologies of the CNS related to plectin have been discovered in patients with plectinopathies. However, in view of plectin as an integrator of a cohesive mesh of cellular proteins, it is important that the role of plectin is also considered in other CNS pathologies. This review summarizes the current knowledge of plectin in the CNS, focusing on plectin isoforms that have been detected in the CNS, along with its expression profile and distribution alongside diverse cytoskeleton filaments in CNS cell types. Considering that the bidirectional communication between neurons and glial cells, especially astrocytes, is crucial for proper functioning of the CNS, we place particular emphasis on the known roles of plectin in neurons, and we propose possible roles of plectin in astrocytes.

scholarly journals Emerging Roles of Extracellular Vesicles in the Central Nervous System: Physiology, Pathology, and Therapeutic Perspectives

2021 ◽  
Vol 15 ◽  
Author(s):  
Yadaly Gassama ◽  
Alexandre Favereaux
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Extracellular Vesicles ◽  
Cell Types ◽  
Cellular Processes ◽  
Pathological Conditions ◽  
The Central Nervous System ◽  
System Physiology ◽  
The Brain

Extracellular vesicles or EVs are secreted by most, if not all, eukaryote cell types and recaptured by neighboring or distant cells. Their cargo, composed of a vast diversity of proteins, lipids, and nucleic acids, supports the EVs’ inter-cellular communication. The role of EVs in many cellular processes is now well documented both in physiological and pathological conditions. In this review, we focus on the role of EVs in the central nervous system (CNS) in physiological as well as pathological conditions such as neurodegenerative diseases or brain cancers. We also discuss the future of EVs in clinical research, in particular, their value as biomarkers as well as innovative therapeutic agents. While an increasing number of studies reveal EV research as a promising field, progress in the standardization of protocols and innovation in analysis as well as in research tools is needed to make a breakthrough in our understanding of their impact in the pathophysiology of the brain.

5. Reacting and thinking

2021 ◽  
pp. 76-88
Author(s):  
Jamie A. Davies
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Learning And Memory ◽  
Cell Types ◽  
The Body ◽  
The Central Nervous System ◽  
The Brain ◽  
Vast Network

This chapter assesses the nervous system. In the trunk of the body and the neck, the central nervous system (CNS) is called the spinal cord; in the head, it is called the brain. The CNS is dominated by two cell types: neurons and glia. The neurons form a vast network in which information is split, combined, and somehow processed. Examples of this processing include reflex arcs, the ‘circuitry’ that detects features such as edges in images coming from the eyes, and simple types of learning and memory. However, most other things in the brain, especially thinking and feeling, are not yet understood at all well.

Adenosine Receptors in Modulation of Central Nervous System Disorders

2019 ◽  
Vol 25 (26) ◽  
pp. 2808-2827 ◽  
Author(s):  
Hira Choudhury ◽  
Dinesh K. Chellappan ◽  
Pallav Sengupta ◽  
Manisha Pandey ◽  
Bapi Gorain
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Adenosine Receptors ◽  
Drug Targets ◽  
Active Components ◽  
Cns Disorders ◽  
The Central Nervous System ◽  
Minimal Concentration ◽  
The Impact ◽  
G Protein Coupled

The ubiquitous signaling nucleoside molecule, adenosine is found in different cells of the human body to provide its numerous pharmacological role. The associated actions of endogenous adenosine are largely dependent on conformational change of the widely expressed heterodimeric G-protein-coupled A1, A2A, A2B, and A3 adenosine receptors (ARs). These receptors are well conserved on the surface of specific cells, where potent neuromodulatory properties of this bioactive molecule reflected by its easy passage through the rigid blood-brainbarrier, to simultaneously act on the central nervous system (CNS). The minimal concentration of adenosine in body fluids (30–300 nM) is adequate to exert its neuromodulatory action in the CNS, whereas the modulatory effect of adenosine on ARs is the consequence of several neurodegenerative diseases. Modulatory action concerning the activation of such receptors in the CNS could be facilitated towards neuroprotective action against such CNS disorders. Our aim herein is to discuss briefly pathophysiological roles of adenosine on ARs in the modulation of different CNS disorders, which could be focused towards the identification of potential drug targets in recovering accompanying CNS disorders. Researches with active components with AR modulatory action have been extended and already reached to the bedside of the patients through clinical research in the improvement of CNS disorders. Therefore, this review consist of recent findings in literatures concerning the impact of ARs on diverse CNS disease pathways with the possible relevance to neurodegeneration.

Functions of the orexinergic/hypocretinergic system

2002 ◽  
Vol 283 (6) ◽  
pp. C1567-C1591 ◽  
Author(s):  
Jyrki P. Kukkonen ◽  
Tomas Holmqvist ◽  
Sylwia Ammoun ◽  
Karl E. O. Åkerman
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Synaptic Activity ◽  
Narrow Region ◽  
Recombinant Receptors ◽  
Orexin Receptors ◽  
Physiological Properties ◽  
The Central Nervous System ◽  
G Protein Coupled ◽  
The Brain

Orexin A and orexin B are hypothalamic peptides that act on their targets via two G protein-coupled receptors (OX1 and OX2 receptors). In the central nervous system, the cell bodies producing orexins are localized in a narrow region within the lateral hypothalamus and project mainly to regions involved in feeding, sleep, and autonomic functions. Via putative pre- and postsynaptic effects, orexins increase synaptic activity in these regions. In isolated neurons and cells expressing recombinant receptors orexins cause Ca2+ elevation, which is mainly dependent on influx. The activity of orexinergic cells appears to be controlled by feeding- and sleep-related signals via a variety of neurotransmitters/hormones from the brain and other tissues. Orexins and orexin receptors are also found outside the central nervous system, particularly in organs involved in feeding and energy metabolism, e.g., gastrointestinal tract, pancreas, and adrenal gland. In the present review we focus on the physiological properties of the cells that secrete or respond to orexins.

scholarly journals Tumors of the Central Nervous System: An Update

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2507
Author(s):  
Carla Mucignat-Caretta
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Structure ◽  
Cell Types ◽  
Structure And Function ◽  
Brain Structure And Function ◽  
The Central Nervous System ◽  
And Function ◽  
Different Cell Types ◽  
The Brain

The brain may be affected by a variety of tumors of different grade, which originate from different cell types at distinct locations, thus impacting on the brain structure and function [...]

Glucuronyl 3-sulfate occurs exclusively on distal unmyelinated terminals of selected sensory neurons in the peripheral nervous system

1995 ◽  
Vol 53 ◽  
pp. 958-959
Author(s):  
S.S. Spicer ◽  
B.A. Schulte
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cerebral Cortex ◽  
Peripheral Nervous System ◽  
Sensory Neurons ◽  
Sensory Nerves ◽  
Tissue Antigens ◽  
The Central Nervous System ◽  
The Brain ◽  
Leu 7

Generation of monoclonal antibodies (MAbs) against tissue antigens has yielded several (VC1.1, HNK- 1, L2, 4F4 and anti-leu 7) which recognize the unique sugar epitope, glucuronyl 3-sulfate (Glc A3- SO4). In the central nervous system, these MAbs have demonstrated Glc A3-SO4 at the surface of neurons in the cerebral cortex, the cerebellum, the retina and other widespread regions of the brain.Here we describe the distribution of Glc A3-SO4 in the peripheral nervous system as determined by immunostaining with a MAb (VC 1.1) developed against antigen in the cat visual cortex. Outside the central nervous system, immunoreactivity was observed only in peripheral terminals of selected sensory nerves conducting transduction signals for touch, hearing, balance and taste. On the glassy membrane of the sinus hair in murine nasal skin, just deep to the ringwurt, VC 1.1 delineated an intensely stained, plaque-like area (Fig. 1). This previously unrecognized structure of the nasal vibrissae presumably serves as a tactile end organ and to our knowledge is not demonstrable by means other than its selective immunopositivity with VC1.1 and its appearance as a densely fibrillar area in H&E stained sections.

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