scholarly journals Is the Exposome Involved in Brain Disorders through the Serotoninergic System?

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1351
Author(s):  
Denis Sarrouilhe ◽  
Norah Defamie ◽  
Marc Mesnil
Keyword(s):  
Serotoninergic System ◽  
Vasoactive Agent ◽  
Neurodevelopmental Toxicity ◽  
Wide Range ◽  
Potential Link ◽  
Common Etiology ◽  
The Central Nervous System ◽  
Health And Disease ◽  
Biogenic Monoamine

Serotonin (5-hydroxytryptamine, 5-HT) is a biogenic monoamine acting as a neurotransmitter in the central nervous system (CNS), local mediator in the gut, and vasoactive agent in the blood. It has been linked to a variety of CNS functions and is implicated in many CNS and psychiatric disorders. The high comorbidity between some neuropathies can be partially understood by the fact that these diseases share a common etiology involving the serotoninergic system. In addition to its well-known functions, serotonin has been shown to be a mitogenic factor for a wide range of normal and tumor cells, including glioma cells, in vitro. The developing CNS of fetus and newborn is particularly susceptible to the deleterious effects of neurotoxic substances in our environment, and perinatal exposure could result in the later development of diseases, a hypothesis known as the developmental origin of health and disease. Some of these substances affect the serotoninergic system and could therefore be the source of a silent pandemic of neurodevelopmental toxicity. This review presents the available data that are contributing to the appreciation of the effects of the exposome on the serotoninergic system and their potential link with brain pathologies (neurodevelopmental, neurodegenerative, neurobehavioral disorders, and glioblastoma).

Orexin 2 Receptor (OX2R) Protein Distribution Measured by Autoradiography Using Radiolabeled OX2R-Selective Antagonist EMPA in Rodent Brain and Peripheral Tissues

2021 ◽  
Author(s):  
Kayo Mitsukawa ◽  
Haruhide Kimura
Keyword(s):  
Brain Slices ◽  
Brain Regions ◽  
Retrosplenial Cortex ◽  
Biological Functions ◽  
Protein Distribution ◽  
Peripheral Tissues ◽  
Physiological Functions ◽  
Wide Range ◽  
The Central Nervous System

Abstract Orexin, a neuropeptide, performs various physiological functions, including the regulation of emotion, feeding, metabolism, respiration, and sleep/wakefulness, by activating the orexin 1 receptor and orexin 2 receptor (OX2R). Owing to the pivotal role of OX2R in wakefulness and other biological functions, OX2R agonists are being developed. A detailed understanding of OX2R protein distribution is essential for determining the mechanisms of action of OX2R agonists; however, this has been hindered by the lack of selective antibodies. In this study, we first confirmed the OX2R-selective binding of [3H]-EMPA in in vitro autoradiography studies, using brain slices from OX2R knockout mice and their wild-type littermates. Subsequently, OX2R protein distribution in rats was comprehensively assessed in 51 brain regions and 10 peripheral tissues using in vitro autoradiography with [3H]-EMPA. The widespread distribution of OX2R protein, including that in previously unrecognized regions of the retrosplenial cortex and suprachiasmatic nucleus of the hypothalamus, was identified. In contrast, negligible/very low OX2R protein expression was observed in peripheral tissues, suggesting that orexin exerts OX2R-dependent physiological functions primarily through activation of the central nervous system. These data would be useful for understanding the wide range of biological functions of OX2R and the application of OX2R agonists in various disorders.

scholarly journals Living Proof of Activity of Extracellular Vesicles in the Central Nervous System

2021 ◽  
Vol 22 (14) ◽  
pp. 7294
Author(s):  
Shadi Mahjoum ◽  
David Rufino-Ramos ◽  
Luís Pereira de Almeida ◽  
Marike L. D. Broekman ◽  
Xandra O. Breakefield ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Extracellular Vesicles ◽  
Optimal Functioning ◽  
Wide Range ◽  
The Central Nervous System ◽  
Rna And Dna

The central nervous system (CNS) consists of a heterogeneous population of cells with highly specialized functions. For optimal functioning of the CNS, in disease and in health, intricate communication between these cells is vital. One important mechanism of cellular communication is the release and uptake of extracellular vesicles (EVs). EVs are membrane enclosed particles actively released by cells, containing a wide array of proteins, lipids, RNA, and DNA. These EVs can be taken up by neighboring or distant cells, and influence a wide range of processes. Due to the complexity and relative inaccessibility of the CNS, our current understanding of the role of EVs is mainly derived in vitro work. However, recently new methods and techniques have opened the ability to study the role of EVs in the CNS in vivo. In this review, we discuss the current developments in our understanding of the role of EVs in the CNS in vivo.

scholarly journals Effect of Gambogic Acid–Loaded Porous-Lipid/PLGA Microbubbles in Combination With Ultrasound-Triggered Microbubble Destruction on Human Glioma

2021 ◽  
Vol 9 ◽  
Author(s):  
Feng Wang ◽  
Lei Dong ◽  
Xixi Wei ◽  
Yongling Wang ◽  
Liansheng Chang ◽  
...  
Keyword(s):  
Focused Ultrasound ◽  
Glioma Cells ◽  
Antitumor Agent ◽  
Gambogic Acid ◽  
Human Glioma ◽  
Human Glioma Cells ◽  
Wide Range ◽  
The Central Nervous System ◽  
Novel Targets

Gambogic acid (GA) is a highly effective antitumor agent, and it is used for the treatment of a wide range of cancers. It is challenging to deliver drugs to the central nervous system due to the inability of GA to cross the blood–brain barrier (BBB). Studies have shown that ultrasound-targeted microbubble destruction can be used for transient and reversible BBB disruption, significantly facilitating intracerebral drug delivery. We first prepared GA–loaded porous-lipid microbubbles (GA porous-lipid/PLGA MBs), and an in vitro BBB model was established. The cell viability was detected by CCK-8 assay and flow cytometry. The results indicate that U251 human glioma cells were killed by focused ultrasound (FUS) combined with GA/PLGA microbubbles. FUS combined with GA/PLGA microbubbles was capable of locally and transiently enhancing the permeability of BBB under certain conditions. This conformational change allows the release of GA to extracellular space. This study provides novel targets for the treatment of glioma.

scholarly journals Hypoxia-Inducible Factor (HIF) in Ischemic Stroke and Neurodegenerative Disease

2021 ◽  
Vol 9 ◽  
Author(s):  
Elena V. Mitroshina ◽  
Maria O. Savyuk ◽  
Evgeni Ponimaskin ◽  
Maria V. Vedunova
Keyword(s):  
Hypoxia Inducible Factor ◽  
Adaptation To Hypoxia ◽  
Adaptation Mechanism ◽  
Physiological Importance ◽  
Work Related ◽  
Hypoxic Environment ◽  
Wide Range ◽  
Liver And Kidney ◽  
The Central Nervous System ◽  
Health And Disease

Hypoxia is one of the most common pathological conditions, which can be induced by multiple events, including ischemic injury, trauma, inflammation, tumors, etc. The body’s adaptation to hypoxia is a highly important phenomenon in both health and disease. Most cellular responses to hypoxia are associated with a family of transcription factors called hypoxia-inducible factors (HIFs), which induce the expression of a wide range of genes that help cells adapt to a hypoxic environment. Basic mechanisms of adaptation to hypoxia, and particularly HIF functions, have being extensively studied over recent decades, leading to the 2019 Nobel Prize in Physiology or Medicine. Based on their pivotal physiological importance, HIFs are attracting increasing attention as a new potential target for treating a large number of hypoxia-associated diseases. Most of the experimental work related to HIFs has focused on roles in the liver and kidney. However, increasing evidence clearly demonstrates that HIF-based responses represent an universal adaptation mechanism in all tissue types, including the central nervous system (CNS). In the CNS, HIFs are critically involved in the regulation of neurogenesis, nerve cell differentiation, and neuronal apoptosis. In this mini-review, we provide an overview of the complex role of HIF-1 in the adaptation of neurons and glia cells to hypoxia, with a focus on its potential involvement into various neuronal pathologies and on its possible role as a novel therapeutic target.

scholarly journals Intestinal Epithelial Organoids as Tools to Study Epigenetics in Gut Health and Disease

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Judith Kraiczy ◽  
Matthias Zilbauer
Keyword(s):  
Intestinal Epithelium ◽  
Cell Function ◽  
Intestinal Epithelial ◽  
Gut Health ◽  
Functional Development ◽  
Functional Aspects ◽  
Wide Range ◽  
Health And Disease ◽  
Human Intestinal Epithelium

The intestinal epithelium forms the inner layer of the human intestine and serves a wide range of diverse functions. Its constant exposure to a vast amount of complex microbiota highlights the critical interface that this single-cell layer forms between the host and our environment. Importantly, the well-documented contribution of environmental factors towards the functional development of the human intestinal epithelium directly implies epigenetic mechanisms in orchestrating this complex interplay. The development of intestinal epithelial organoid culture systems that can be generated from human tissue provides researchers with unpresented opportunities to study functional aspects of human intestinal epithelial pathophysiology. In this brief review, we summarise existing evidence for the role of epigenetics in regulating intestinal epithelial cell function and highlight the great potential for human gut organoids as translational research tools to investigate these mechanisms in vitro.

scholarly journals Scanning Various Nanomaterials and Variable Camouflages to Evaluate the Biocompatibility in Multi-organs of Embryos

2020 ◽  
Author(s):  
Bin Zheng ◽  
Mingming Guo ◽  
Meijun Pang ◽  
Dong Ming
Keyword(s):  
Safety Assessment ◽  
Silica Coating ◽  
Toxicity Assessment ◽  
Specific Cell ◽  
Cdse Qds ◽  
Multiple Organs ◽  
Wide Range ◽  
Health And Disease

Abstract Background:Nanomaterials are under a wide range of application prospects in human health and disease, such as medical imaging and drug delivery and treatment. With the gradual advent of the nano era, the safety of nanomaterials in biology must be evaluated more widely and deeply. Therefore, superficial safety assessment based on specific cell lines in vitro is difficult to meet the current needs. Multi-organs assessment in vivo will be beneficial in establishing a more comprehensive pathway for the understanding of nanomaterials-induced biotoxicity. Results:In this work, we employed a series of genetically modified zebrafish models for nanomaterials toxicity assessment. The results demonstrated that cadmium selenide (CdSe) quantum dot (QDs) was the most toxic after scanning some popular nanomaterials. Among modified methods of silica coating, core-shell structure development and organic molecular camouflage, the polyethylene glycol camouflage method exhibits a better performance of improving the biocompatibility of CdSe QDs in multiple-organs including hearts, nerves, blood vessels, and immune system. Conclusion:Our work provides an alternative paradigm for more in-depth and sensitive preclinical validation of biocompatibility, especially in neurotoxicity and cardiotoxicity of embryos, and a guidance for reducing the toxicity of biomedical materials.

scholarly journals Maternal exposure to polystyrene nanoplastics causes brain abnormalities in progeny

2021 ◽  
Author(s):  
Bohyeon Jeong ◽  
Young-Kyoung Ryu ◽  
Jeong Yeob Baek ◽  
Jahong Koo ◽  
Subin Park ◽  
...  
Keyword(s):  
Developmental Stages ◽  
Environmental Concern ◽  
Biological Effects ◽  
In Vitro Study ◽  
Wide Range ◽  
The Central Nervous System ◽  
High Concentrations ◽  
Living Organisms ◽  
Maternal Administration

Abstract As global plastic production continues to grow, microplastics released from a massive quantity of plastic wastes have become a critical environmental concern. These microplastic particles are found in a wide range of living organisms in a diverse array of ecosystems. In this study, we investigated the biological effects of polystyrene nanoplastics (PSNPs) on development of the central nervous system using cultured neural stem cells (NSCs) and mice exposed to PSNPs during developmental stages. Our study demonstrates that maternal administration of PSNPs during gestation and lactating periods altered the functioning of NSCs, neural cell compositions, and brain histology in progeny. Similarly, our in vitro study also shows PSNP-induced molecular and functional defects in NSCs. Finally, we show that the abnormal brain development caused by exposure to high concentrations of PSNPs results in neurophysiological and cognitive deficits in a gender-specific manner. Our data demonstrate the possibility that exposure to high amounts of PSNPs may increase the risk of neurodevelopmental defects.

Evaluation of 99mTc-Label led Vitamin K4 as an Agent for Testicular Imaging

1991 ◽  
Vol 30 (01) ◽  
pp. 35-39 ◽  
Author(s):  
H. S. Durak ◽  
M. Kitapgi ◽  
B. E. Caner ◽  
R. Senekowitsch ◽  
M. T. Ercan
Keyword(s):  
Soft Tissue ◽  
Room Temperature ◽  
Normal Subjects ◽  
Left Testis ◽  
Wide Range ◽  
Activity Ratios ◽  
The Right ◽  
Radioactivity Levels

Vitamin K4 was labelled with 99mTc with an efficiency higher than 97%. The compound was stable up to 24 h at room temperature, and its biodistribution in NMRI mice indicated its in vivo stability. Blood radioactivity levels were high over a wide range. 10% of the injected activity remained in blood after 24 h. Excretion was mostly via kidneys. Only the liver and kidneys concentrated appreciable amounts of radioactivity. Testis/soft tissue ratios were 1.4 and 1.57 at 6 and 24 h, respectively. Testis/blood ratios were lower than 1. In vitro studies with mouse blood indicated that 33.9 ±9.6% of the radioactivity was associated with RBCs; it was washed out almost completely with saline. Protein binding was 28.7 ±6.3% as determined by TCA precipitation. Blood clearance of 99mTc-l<4 in normal subjects showed a slow decrease of radioactivity, reaching a plateau after 16 h at 20% of the injected activity. In scintigraphic images in men the testes could be well visualized. The right/left testis ratio was 1.08 ±0.13. Testis/soft tissue and testis/blood activity ratios were highest at 3 h. These ratios were higher than those obtained with pertechnetate at 20 min post injection.99mTc-l<4 appears to be a promising radiopharmaceutical for the scintigraphic visualization of testes.

In Vitro Clot Lysis as a Potential Indicator of Thrombus Resistance to Fibrinolysis – Study in Healthy Subjects and Correlation with Blood Fibrinolytic Parameters

1997 ◽  
Vol 77 (04) ◽  
pp. 725-729 ◽  
Author(s):  
Mario Colucci ◽  
Silvia Scopece ◽  
Antonio V Gelato ◽  
Donato Dimonte ◽  
Nicola Semeraro
Keyword(s):  
Plasminogen Activator ◽  
Clot Lysis ◽  
Individual Response ◽  
Plasminogen Activator Inhibitor 1 ◽  
Autologous Plasma ◽  
Wide Range ◽  
Blood Clots ◽  
Physiological Variations ◽  
Pai 1

SummaryUsing an in vitro model of clot lysis, the individual response to a pharmacological concentration of recombinant tissue plasminogen activator (rt-PA) and the influence on this response of the physiological variations of blood parameters known to interfere with the fibrinolytic/thrombolytic process were investigated in 103 healthy donors. 125I-fibrin labelled blood clots were submersed in autologous plasma, supplemented with 500 ng/ml of rt-PA or solvent, and the degree of lysis was determined after 3 h of incubation at 37° C. Baseline plasma levels of t-PA, plasminogen activator inhibitor 1 (PAI-1), plasminogen, α2-anti-plasmin, fibrinogen, lipoprotein (a), thrombomodulin and von Willebrand factor as well as platelet and leukocyte count and clot retraction were also determined in each donor. rt-PA-induced clot lysis varied over a wide range (28-75%) and was significantly related to endogenous t-PA, PAI-1, plasminogen (p <0.001) and age (p <0.01). Multivariate analysis indicated that both PAI-1 antigen and plasminogen independently predicted low response to rt-PA. Surprisingly, however, not only PAI-1 but also plasminogen was negatively correlated with rt-PA-ginduced clot lysis. The observation that neutralization of PAI-1 by specific antibodies, both in plasma and within the clot, did not potentiate clot lysis indicates that the inhibitor, including the platelet-derived form, is insufficient to attenuate the thrombolytic activity of a pharmacological concentration of rt-PA and that its elevation, similarly to the elevation of plasminogen, is not the cause of clot resistance but rather a coincident finding. It is concluded that the in vitro response of blood clots to rt-PA is poorly influenced by the physiological variations of the examined parameters and that factors other than those evaluated in this study interfere with clot dissolution by rt-PA. In vitro clot lysis test might help to identify patients who may be resistant to thrombolytic therapy.

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