scholarly journals P2X7 Receptor Signaling in Stress and Depression

2019 ◽  
Vol 20 (11) ◽  
pp. 2778 ◽  
Author(s):  
Deidiane Elisa Ribeiro ◽  
Aline Lulho Roncalho ◽  
Talita Glaser ◽  
Henning Ulrich ◽  
Gregers Wegener ◽  
...  
Keyword(s):  
P2x7 Receptor ◽  
Neuronal Degeneration ◽  
Cell Types ◽  
Innate Immune ◽  
Gene Encoding ◽  
Pyrin Domain ◽  
Pharmacological Targets ◽  
Treatment Of Depression ◽  
The Central Nervous System ◽  
Different Cell Types

Stress exposure is considered to be the main environmental cause associated with the development of depression. Due to the limitations of currently available antidepressants, a search for new pharmacological targets for treatment of depression is required. Recent studies suggest that adenosine triphosphate (ATP)-mediated signaling through the P2X7 receptor (P2X7R) might play a prominent role in regulating depression-related pathology, such as synaptic plasticity, neuronal degeneration, as well as changes in cognitive and behavioral functions. P2X7R is an ATP-gated cation channel localized in different cell types in the central nervous system (CNS), playing a crucial role in neuron-glia signaling. P2X7R may modulate the release of several neurotransmitters, including monoamines, nitric oxide (NO) and glutamate. Moreover, P2X7R stimulation in microglia modulates the innate immune response by activating the NLR family pyrin domain containing 3 (NLRP3) inflammasome, consistent with the neuroimmune hypothesis of MDD. Importantly, blockade of P2X7R leads to antidepressant-like effects in different animal models, which corroborates the findings that the gene encoding for the P2X7R is located in a susceptibility locus of relevance to depression in humans. This review will discuss recent findings linked to the P2X7R involvement in stress and MDD neuropathophysiology, with special emphasis on neurochemical, neuroimmune, and neuroplastic mechanisms.

scholarly journals CD77 levels over enzyme replacement treatment in Fabry Disease Family (V269M)

2018 ◽  
Vol 40 (4) ◽  
pp. 333-338
Author(s):  
Ester Miranda Pereira ◽  
Adalberto Socorro da Silva ◽  
Raimundo Nonato da Silva ◽  
José Tiburcio Monte Neto ◽  
Fernando F. do Nascimento ◽  
...  
Keyword(s):  
Fabry Disease ◽  
Cell Types ◽  
Control Group ◽  
Gene Encoding ◽  
Peripheral Blood Mononuclear ◽  
Enzyme Replacement ◽  
Replacement Treatment ◽  
Promising Tool ◽  
Potential Marker ◽  
Different Cell Types

ABSTRACT Introduction: Fabry disease (FD) is a disorder caused by mutations in the gene encoding for lysosomal enzyme α-galactosidase A (α-GAL). Reduced α-GAL activity leads to progressive accumulation of globotriaosylceramide (Gb3), also known as CD77. The recent report of increased expression of CD77 in blood cells of patients with FD indicated that this molecule can be used as a potential marker for monitoring enzyme replacement therapy (ERT). Objective: The purpose of this study was to evaluate the CD77 levels throughout ERT in FD patients (V269M mutation). Methods: We evaluated the fluctuations in PBMC (peripheral blood mononuclear cell) membrane CD77 expression in FD patients undergoing ERT and correlated these levels with those observed in different cell types. Results: A greater CD77 expression was found in phagocytes of patients compared to controls at baseline. Interestingly, the variability in CD77 levels is larger in patients at baseline (340 - 1619 MIF) and after 12 months of ERT (240 - 530 MIF) compared with the control group (131 - 331 MFI). Furthermore, by analyzing the levels of CD77 in phagocytes from patients throughout ERT, we found a constant decrease in CD77 levels. Conclusion: The increased CD77 levels in the phagocytes of Fabry carriers together with the decrease in CD77 levels throughout ERT suggest that measuring CD77 levels in phagocytes is a promising tool for monitoring the response to ERT in FD.

Neuroanatomy and neurophysiology

2021 ◽  
pp. 725-852
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cervical Vertebrae ◽  
Lymphatic Vessels ◽  
Cell Types ◽  
Cellular Level ◽  
Inhibitory Synapses ◽  
The Central Nervous System ◽  
Emotion Memory ◽  
Different Cell Types

‘Neuroanatomy and neurophysiology’ covers the anatomy and organization of the central nervous system, including the skull and cervical vertebrae, the meninges, the blood and lymphatic vessels, muscles and nerves of the head and neck, and the structures of the eye, ear, and central nervous system. At a cellular level, the different cell types and the mechanism of transmission across synapses are considered, including excitatory and inhibitory synapses. This is followed by a review of the major control and sensory systems (including movement, information processing, locomotion, reflexes, and the main five senses of sight, hearing, touch, taste, and smell). The integration of these processes into higher functions (such as sleep, consciousness and coma, emotion, memory, and ageing) is discussed, along with the causes and treatments of disorders of diseases such as depression, schizophrenia, epilepsy, addiction, and degenerative diseases.

Mucopolysaccharidosis in Adults

2016 ◽  
Author(s):  
Christian J. Hendriksz ◽  
Francois Karstens
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Autosomal Recessive ◽  
Clinical Symptoms ◽  
Cell Types ◽  
Type Ii ◽  
System P ◽  
Different Types ◽  
The Central Nervous System ◽  
Different Cell Types

There are 8 different types of diseases of the mucopolysaccharides, each caused by a deficiency in one of 10 different enzymes involved in the degradation of glycosaminoglycans (GAGs). Partially degraded GAGs accumulate within the lysosomes of many different cell types and lead to clinical symptoms and excretion of large amounts of GAGs in the urine. Heritability is autosomal recessive except for MPS type II, which is X-linked. The disorders are chronic and progressive and, although the specific types all have their individual features, they share an abundance of clinical similarities. All involve the musculoskeletal, the cardiovascular, the pulmonary and the central nervous system.

scholarly journals Engineering advanced logic and distributed computing in human CAR immune cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jang Hwan Cho ◽  
Atsushi Okuma ◽  
Katri Sofjan ◽  
Seunghee Lee ◽  
James J. Collins ◽  
...  
Keyword(s):  
Immune Cells ◽  
Communication Channel ◽  
Immune Cell ◽  
Cell Types ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Complex Phenotypes ◽  
Car T ◽  
Different Cell Types ◽  
Multiple Immune Cell

AbstractThe immune system is a sophisticated network of different cell types performing complex biocomputation at single-cell and consortium levels. The ability to reprogram such an interconnected multicellular system holds enormous promise in treating various diseases, as exemplified by the use of chimeric antigen receptor (CAR) T cells as cancer therapy. However, most CAR designs lack computation features and cannot reprogram multiple immune cell types in a coordinated manner. Here, leveraging our split, universal, and programmable (SUPRA) CAR system, we develop an inhibitory feature, achieving a three-input logic, and demonstrate that this programmable system is functional in diverse adaptive and innate immune cells. We also create an inducible multi-cellular NIMPLY circuit, kill switch, and a synthetic intercellular communication channel. Our work highlights that a simple split CAR design can generate diverse and complex phenotypes and provide a foundation for engineering an immune cell consortium with user-defined functionalities.

scholarly journals Reversible ubiquitination shapes NLRC5 function and modulates NF-κB activation switch

2015 ◽  
Vol 211 (5) ◽  
pp. 1025-1040 ◽  
Author(s):  
Qingcai Meng ◽  
Chunmei Cai ◽  
Tingzhe Sun ◽  
Qianliang Wang ◽  
Weihong Xie ◽  
...  
Keyword(s):  
Dynamic Control ◽  
Cell Types ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Polyubiquitin Chains ◽  
Iκb Kinase ◽  
Dynamic Modification ◽  
Important Regulator ◽  
Mathematical Analyses ◽  
Different Cell Types

NLRC5 is an important regulator in innate immune responses. However, the ability of NLRC5 to inhibit NF-κB activation is controversial in different cell types. How dynamic modification of NLRC5 shapes NF-κB signaling remains unknown. We demonstrated that NLRC5 undergoes robust ubiquitination by TRAF2/6 after lipopolysaccharide treatment, which leads to dissociation of the NLRC5–IκB kinase complex. Experimental and mathematical analyses revealed that the K63-linked ubiquitination of NLRC5 at lysine 1,178 generates a coherent feedforward loop to further sensitize NF-κB activation. Meanwhile, we found USP14 specifically removes the polyubiquitin chains from NLRC5 to enhance NLRC5-mediated inhibition of NF-κB signaling. Furthermore, we found that different cell types may exhibit different sensitivities to NF-κB activation in response to NLRC5 ablation, possibly as a result of the various intrinsic levels of deubiquitinases and NLRC5. This might partially reconcile controversial studies and explain why NLRC5 exhibits diverse inhibitory efficiencies. Collectively, our results provide the regulatory mechanisms of reversible NLRC5 ubiquitination and its role in the dynamic control of innate immunity.

scholarly journals Lithium: Immunomodulatory and Anti-Infectious Activities

2019 ◽  
Vol 4 (1) ◽  
Keyword(s):  
Immune System ◽  
Inflammatory Cytokines ◽  
Human Body ◽  
Innate Immune System ◽  
Cell Types ◽  
Innate Immune ◽  
Signalling Pathways ◽  
Disease Models ◽  
Absolute Requirement ◽  
Different Cell Types

Lithium (Li), a well-known immunomodulatory agent, has been in use for the treatment of several infectious diseases. Li mainly acts through GSK3β inactivation and several other signalling pathways, which are directly involved in the activation of innate immune system. Li therapy has been shown to cause effective modulation of various inflammatory cytokines, and has also been shown to boost immunity in several disease models. Apart from treatment for mania, Li has also been proved to be effective against infections caused by viruses, bacteria, parasites, and certain life-style disorders. Its effects, ranging from common defensive capabilities to complex pathways for protection of human body, make Li extraordinary. Thus, Li is an absolute requirement that can be a solution for some of the immune related disorders. This review mainly focuses on pharmacology, immune reactions of different cell types, and anti-infectious activities of Li.

Cholesterol in Brain Development and Perinatal Brain Injury: more than a Building Block

2021 ◽  
Vol 19 ◽  
Author(s):  
Fuxin Lu ◽  
Donna M Ferriero ◽  
Xiangning Jiang
Keyword(s):  
Brain Injury ◽  
Brain Development ◽  
Cholesterol Biosynthesis ◽  
Cell Types ◽  
Cholesterol Homeostasis ◽  
Adult Brain ◽  
Brain Maturation ◽  
Perinatal Brain Injury ◽  
The Central Nervous System ◽  
Different Cell Types

: The central nervous system (CNS) is enriched with important classes of lipids, in which cholesterol is known to make up a major portion of myelin sheaths, besides being a structural and functional unit of CNS cell membranes. Unlike in the adult brain where the cholesterol pool is relatively stable, cholesterol is synthesized and accumulated at the highest rate in the developing brain to meet the needs of rapid brain growth at this stage, which is also a critical period for neuroplasticity. In addition to its biophysical role in membrane organization, cholesterol is crucial for brain development due to its involvement in brain patterning, myelination, neuronal differentiation and synaptogenesis. Thus any injuries to the immature brain that affect cholesterol homeostasis may have long-term adverse neurological consequences. In this review, we describe the unique features of brain cholesterol biosynthesis and metabolism, cholesterol trafficking between different cell types, and highlight cholesterol-dependent biological processes during brain maturation. We also discuss the association of impaired cholesterol homeostasis with several forms of perinatal brain disorders in term and preterm newborns, including hypoxic-ischemic encephalopathy. Strategies targeting the cholesterol pathways may open new avenues for diagnosis and treatment of developmental brain injury.

The innate immune system

2020 ◽  
pp. 307-314
Author(s):  
Paul Bowness
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Innate Immune System ◽  
Cell Types ◽  
Innate Immune ◽  
Microbial Pathogens ◽  
Innate Immune Responses ◽  
Adaptive Immune ◽  
System P ◽  
Different Cell Types

The innate immune system comprises evolutionarily ancient mechanisms that mediate first-line responses against microbial pathogens, and are also important in priming and execution of adaptive immune responses, and in defence against tumours. These responses, which recognize microbial non-self, damaged self, and absent self, are characterized by rapidity of action and they involve various different cell types, cell-associated receptors, and soluble factors. Previously thought to lack plasticity or memory, certain innate immune responses have recently been shown to be capable of ‘learning’ or ‘training’. Most cells of the innate immune system are derived from the myeloid precursors in the bone marrow. These include monocytes and their derivatives—macrophages and dendritic cells, blood granulocytes (neutrophils, basophils, and eosinophils), and tissue mast cells.

Dynamin Superfamily at Pre- and Postsynapses: Master Regulators of Synaptic Transmission and Plasticity in Health and Disease

2020 ◽  
pp. 107385842097431
Author(s):  
Jorge Arriagada-Diaz ◽  
Lorena Prado-Vega ◽  
Ana M. Cárdenas Díaz ◽  
Alvaro O. Ardiles ◽  
Arlek M. Gonzalez-Jamett
Keyword(s):  
Synaptic Transmission ◽  
Neurological Disorders ◽  
Synaptic Vesicles ◽  
Cell Types ◽  
Master Regulators ◽  
Vesicle Recycling ◽  
Cytoskeleton Remodeling ◽  
The Central Nervous System ◽  
Health And Disease ◽  
Different Cell Types

Dynamin superfamily proteins (DSPs) comprise a large group of GTP-ases that orchestrate membrane fusion and fission, and cytoskeleton remodeling in different cell-types. At the central nervous system, they regulate synaptic vesicle recycling and signaling-receptor turnover, allowing the maintenance of synaptic transmission. In the presynapses, these GTP-ases control the recycling of synaptic vesicles influencing the size of the ready-releasable pool and the release of neurotransmitters from nerve terminals, whereas in the postsynapses, they are involved in AMPA-receptor trafficking to and from postsynaptic densities, supporting excitatory synaptic plasticity, and consequently learning and memory formation. In agreement with these relevant roles, an important number of neurological disorders are associated with mutations and/or dysfunction of these GTP-ases. Along the present review we discuss the importance of DSPs at synapses and their implication in different neuropathological contexts.

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