The Endocannabinoid System in Glial Cells and Their Profitable Interactions to Treat Epilepsy: Evidence from Animal Models

Epilepsy is one of the most common neurological conditions. Yearly, five million people are diagnosed with epileptic-related disorders. The neuroprotective and therapeutic effect of (endo)cannabinoid compounds has been extensively investigated in several models of epilepsy. Therefore, the study of specific cell-type-dependent mechanisms underlying cannabinoid effects is crucial to understanding epileptic disorders. It is estimated that about 100 billion neurons and a roughly equal number of glial cells co-exist in the human brain. The glial population is in charge of neuronal viability, and therefore, their participation in brain pathophysiology is crucial. Furthermore, glial malfunctioning occurs in a wide range of neurological disorders. However, little is known about the impact of the endocannabinoid system (ECS) regulation over glial cells, even less in pathological conditions such as epilepsy. In this review, we aim to compile the existing knowledge on the role of the ECS in different cell types, with a particular emphasis on glial cells and their impact on epilepsy. Thus, we propose that glial cells could be a novel target for cannabinoid agents for treating the etiology of epilepsy and managing seizure-like disorders.

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mPRs represent a novel target for PRL inhibition in experimental prolactinomas

Endocrine Related Cancer ◽

10.1530/erc-18-0409 ◽

2019 ◽

Vol 26 (5) ◽

pp. 497-510 ◽

Cited By ~ 2

Author(s):

María Andrea Camilletti ◽

Alejandra Abeledo-Machado ◽

Pablo A Perez ◽

Erika Y Faraoni ◽

Fernanda De Fino ◽

...

Keyword(s):

Relative Proportion ◽

Progesterone Receptors ◽

Cell Types ◽

Prolactin Secretion ◽

Dopaminergic Drugs ◽

Rat Pituitary ◽

Novel Target ◽

Different Cell Types

Membrane progesterone receptors are known to mediate rapid nongenomic progesterone effects in different cell types. Recent evidence revealed that mPRα is highly expressed in the rat pituitary, being primarily localized in lactotrophs, acting as an intermediary of P4-inhibitory actions on prolactin secretion. The role of mPRs in prolactinoma development remains unclear. We hypothesize that mPR agonists represent a novel tool for hyperprolactinemia treatment. To this end, pituitary expression of mPRs was studied in three animal models of prolactinoma. Expression of mPRs and nuclear receptor was significantly decreased in tumoral pituitaries compared to normal ones. However, the relative proportion of mPRα and mPRβ was highly increased in prolactinomas. Interestingly, the selective mPR agonist (Org OD 02-0) significantly inhibited PRL release in both normal and tumoral pituitary explants, displaying a more pronounced effect in tumoral tissues. As P4 also regulates PRL secretion indirectly, by acting on dopaminergic neurons, we studied mPR involvement in this effect. We found that the hypothalamus has a high expression of mPRs. Interestingly, both P4 and OrgOD 02-0 increased dopamine release in hypothalamus explants. Moreover, in an in vivo treatment, that allows both, pituitary and hypothalamus actions, the mPR agonist strongly reduced the hyperprolactinemia in transgenic females carrying prolactinoma. Finally, we also found and interesting gender difference: males express higher levels of pituitary mPRα/β, a sex that does not develop prolactinoma in these mice models. Taken together, these findings suggest mPRs activation could represent a novel tool for hyperprolactinemic patients, especially those that present resistance to dopaminergic drugs.

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In vitro studies of glial cells: what can we learn about demyelinating diseases?

Multiple Sclerosis Journal ◽

10.1177/135245859600200402 ◽

1996 ◽

Vol 2 (4) ◽

pp. 173-178 ◽

Cited By ~ 1

Author(s):

Robert P Lisak

Keyword(s):

Glial Cells ◽

Cell Types ◽

Demyelinating Diseases ◽

Unknown Etiology ◽

Specific Cell ◽

Neurologic Diseases ◽

Important Group ◽

Glial Cell Cultures

Acquired demyelinating diseases of the central and peripheral nervous systems comprise an important group of neurologic diseases of unknown etiology and incompletely understood pathogenesis. Cultures of glial cells are proving highly useful in investigating the role of both antibodies and cytokines in the pathogenesis of these disorders. While there clearly is need for comparative studies employing more complex systems and using patient derived tissues, glial cell cultures provide important advantages by allowing researchers to characterize the effect of cytokines and growth factors on specific cell types in controlled conditions.

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Role of Transcriptional Read-Through in PRE Activity in Drosophila melanogaster

Acta Naturae ◽

10.32607/20758251-2016-8-2-79-86 ◽

2016 ◽

Vol 8 (2) ◽

pp. 79-86 ◽

Cited By ~ 3

Author(s):

P. V. Elizar’ev ◽

D. V. Lomaev ◽

D. A. Chetverina ◽

P. G. Georgiev ◽

M. M. Erokhin

Keyword(s):

Dna Sequences ◽

Cell Types ◽

Transcription Terminator ◽

Response Elements ◽

Polycomb Response Elements ◽

The Individual ◽

Multicellular Organisms ◽

Different Cell Types ◽

Main Factor

Maintenance of the individual patterns of gene expression in different cell types is required for the differentiation and development of multicellular organisms. Expression of many genes is controlled by Polycomb (PcG) and Trithorax (TrxG) group proteins that act through association with chromatin. PcG/TrxG are assembled on the DNA sequences termed PREs (Polycomb Response Elements), the activity of which can be modulated and switched from repression to activation. In this study, we analyzed the influence of transcriptional read-through on PRE activity switch mediated by the yeast activator GAL4. We show that a transcription terminator inserted between the promoter and PRE doesnt prevent switching of PRE activity from repression to activation. We demonstrate that, independently of PRE orientation, high levels of transcription fail to dislodge PcG/TrxG proteins from PRE in the absence of a terminator. Thus, transcription is not the main factor required for PRE activity switch.

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History and Morality

10.1093/oso/9780198858713.001.0001 ◽

2020 ◽

Author(s):

Donald Bloxham

Keyword(s):

Foreign Country ◽

Moral Thought ◽

Majority Opinion ◽

The Past ◽

Wide Range ◽

Moral Judgements ◽

Value Judgements ◽

The Impact

Against majority opinion within his profession, Donald Bloxham argues that it is legitimate, often unavoidable, and frequently important for historians to make value judgements about the past. History and Morality draws on a wide range of historical examples, and its author’s insights as a practising historian. Examining concepts like impartiality, neutrality, contextualization, and the use and abuse of the idea of the past as a foreign country, Bloxham’s book investigates how the discipline has got to the point where what is preached can be so inconsistent with what is practised. It illuminates how far tacit moral judgements infuse works of history, and how strange those histories would look if the judgements were removed. Bloxham argues that rather than trying to eradicate all judgemental elements from their work historians need to think more consistently about how, and with what justification, they make the judgements that they do. The importance of all this lies not just in the responsibilities that historians bear towards the past—responsibilities to take historical actors on those actors’ own terms and to portray the impact of those actors’ deeds—but also in the role of history as a source of identity, pride, and shame in the present. The account of moral thought in History and Morality has ramifications far beyond the activities of vocational historians.

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The Microbiota–Gut–Brain Axis and Alzheimer Disease. From Dysbiosis to Neurodegeneration: Focus on the Central Nervous System Glial Cells

Journal of Clinical Medicine ◽

10.3390/jcm10112358 ◽

2021 ◽

Vol 10 (11) ◽

pp. 2358

Author(s):

Maria Grazia Giovannini ◽

Daniele Lana ◽

Chiara Traini ◽

Maria Giuliana Vannucchi

Keyword(s):

Alzheimer Disease ◽

Glial Cells ◽

Cell Types ◽

The Past ◽

The Central Nervous System ◽

Diseased State ◽

The Brain ◽

Alzheimer Disease Pathogenesis ◽

Brain Homeostasis

The microbiota–gut system can be thought of as a single unit that interacts with the brain via the “two-way” microbiota–gut–brain axis. Through this axis, a constant interplay mediated by the several products originating from the microbiota guarantees the physiological development and shaping of the gut and the brain. In the present review will be described the modalities through which the microbiota and gut control each other, and the main microbiota products conditioning both local and brain homeostasis. Much evidence has accumulated over the past decade in favor of a significant association between dysbiosis, neuroinflammation and neurodegeneration. Presently, the pathogenetic mechanisms triggered by molecules produced by the altered microbiota, also responsible for the onset and evolution of Alzheimer disease, will be described. Our attention will be focused on the role of astrocytes and microglia. Numerous studies have progressively demonstrated how these glial cells are important to ensure an adequate environment for neuronal activity in healthy conditions. Furthermore, it is becoming evident how both cell types can mediate the onset of neuroinflammation and lead to neurodegeneration when subjected to pathological stimuli. Based on this information, the role of the major microbiota products in shifting the activation profiles of astrocytes and microglia from a healthy to a diseased state will be discussed, focusing on Alzheimer disease pathogenesis.

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Optimizing expression quantitative trait locus mapping workflows for single-cell studies

Genome Biology ◽

10.1186/s13059-021-02407-x ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Anna S. E. Cuomo ◽

Giordano Alvari ◽

Christina B. Azodi ◽

Davis J. McCarthy ◽

Marc Jan Bonder ◽

...

Keyword(s):

Gene Expression ◽

Quantitative Trait Locus ◽

Single Cell ◽

Quantitative Trait ◽

Cell Types ◽

Expression Quantitative Trait Locus ◽

Eqtl Mapping ◽

Trait Locus ◽

The Impact

Abstract Background Single-cell RNA sequencing (scRNA-seq) has enabled the unbiased, high-throughput quantification of gene expression specific to cell types and states. With the cost of scRNA-seq decreasing and techniques for sample multiplexing improving, population-scale scRNA-seq, and thus single-cell expression quantitative trait locus (sc-eQTL) mapping, is increasingly feasible. Mapping of sc-eQTL provides additional resolution to study the regulatory role of common genetic variants on gene expression across a plethora of cell types and states and promises to improve our understanding of genetic regulation across tissues in both health and disease. Results While previously established methods for bulk eQTL mapping can, in principle, be applied to sc-eQTL mapping, there are a number of open questions about how best to process scRNA-seq data and adapt bulk methods to optimize sc-eQTL mapping. Here, we evaluate the role of different normalization and aggregation strategies, covariate adjustment techniques, and multiple testing correction methods to establish best practice guidelines. We use both real and simulated datasets across single-cell technologies to systematically assess the impact of these different statistical approaches. Conclusion We provide recommendations for future single-cell eQTL studies that can yield up to twice as many eQTL discoveries as default approaches ported from bulk studies.

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Therapeutic Attributes of Endocannabinoid System against Neuro-Inflammatory Autoimmune Disorders

Molecules ◽

10.3390/molecules26113389 ◽

2021 ◽

Vol 26 (11) ◽

pp. 3389

Author(s):

Ishtiaq Ahmed ◽

Saif Ur Rehman ◽

Shiva Shahmohamadnejad ◽

Muhammad Anjum Zia ◽

Muhammad Ahmad ◽

...

Keyword(s):

Cannabinoid Receptors ◽

Cannabinoid Receptor ◽

Therapeutic Potential ◽

Endocannabinoid System ◽

Cell Types ◽

Autoimmune Disorders ◽

Specific Receptors ◽

Different Cell Types

In humans, various sites like cannabinoid receptors (CBR) having a binding affinity with cannabinoids are distributed on the surface of different cell types, where endocannabinoids (ECs) and derivatives of fatty acid can bind. The binding of these substance(s) triggers the activation of specific receptors required for various physiological functions, including pain sensation, memory, and appetite. The ECs and CBR perform multiple functions via the cannabinoid receptor 1 (CB1); cannabinoid receptor 2 (CB2), having a key effect in restraining neurotransmitters and the arrangement of cytokines. The role of cannabinoids in the immune system is illustrated because of their immunosuppressive characteristics. These characteristics include inhibition of leucocyte proliferation, T cells apoptosis, and induction of macrophages along with reduced pro-inflammatory cytokines secretion. The review seeks to discuss the functional relationship between the endocannabinoid system (ECS) and anti-tumor characteristics of cannabinoids in various cancers. The therapeutic potential of cannabinoids for cancer—both in vivo and in vitro clinical trials—has also been highlighted and reported to be effective in mice models in arthritis for the inflammation reduction, neuropathic pain, positive effect in multiple sclerosis and type-1 diabetes mellitus, and found beneficial for treating in various cancers. In human models, such studies are limited; thereby, further research is indispensable in this field to get a conclusive outcome. Therefore, in autoimmune disorders, therapeutic cannabinoids can serve as promising immunosuppressive and anti-fibrotic agents.

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Differential Pathways of Angiotensin II-Induced Extracellularly Regulated Kinase 1/2 Phosphorylation in Specific Cell Types: Role of Heparin-Binding Epidermal Growth Factor

Molecular Endocrinology ◽

10.1210/me.2003-0476 ◽

2004 ◽

Vol 18 (8) ◽

pp. 2035-2048 ◽

Cited By ~ 62

Author(s):

Bukhtiar H. Shah ◽

Akin Yesilkaya ◽

J. Alberto Olivares-Reyes ◽

Hung-Dar Chen ◽

László Hunyady ◽

...

Keyword(s):

Angiotensin Ii ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Cell Types ◽

Specific Cell ◽

Heparin Binding ◽

Epidermal Growth

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An Overview of the Latest Applications of Platelet-Derived Microparticles and Nanoparticles in Medical Technology 2010-2020

Current Molecular Medicine ◽

10.2174/1566524021666210928152015 ◽

2021 ◽

Vol 21 ◽

Author(s):

Tahereh Zadeh Mehrizi

Keyword(s):

Drug Delivery ◽

Cell Types ◽

Current Status ◽

Target Cells ◽

Interesting Point ◽

Large Size ◽

Review Study ◽

Cellular Pathways ◽

Different Cell Types

: Today, Platelets and platelet-derived nanoparticles and microparticles have found many applications in nanomedical technology. The results of our review study show that no article has been published in this field to review the current status of applications of these platelet derivatives so far. Therefore, in present study, our goal is to compare the applications of platelet derivatives and review their latest status between 2010 and 2020 to present the latest findings to researchers. A very interesting point about the role of platelet derivatives is the presence of molecules on their surface which makes them capable of hiding from the immune system, reaching different target cells, and specifically attaching to different cell types. According to the results of this study, most of their applications include drug delivery, diagnosis of various diseases, and tissue engineering. However, their application in drug delivery is limited due to heterogeneity, large size, and the possibility of interference with cellular pathways in microparticles derived from other cells. On the other hand, platelet nanoparticles are more controllable and have been widely used for drug delivery in treatment of cancer, atherosclerosis, thrombosis, infectious diseases, repair of damaged tissue, and photothermal therapy. The results of this study show that platelet nanoparticles are more controllable than platelet microparticles and have a higher potential for use in medicine.

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Measurements of cell adhesion

Development ◽

10.1242/dev.30.2.499 ◽

1973 ◽

Vol 30 (2) ◽

pp. 499-509

Author(s):

Janet E. Hornby

Keyword(s):

Cell Types ◽

Random Motion ◽

Chick Embryos ◽

Collision Efficiency ◽

20 Nm ◽

Kidney Liver ◽

Different Cell Types ◽

Laminar Shear ◽

Lyophobic Sols

Cell suspensions were prepared from the kidney, liver and heart of chick embryos of 5 or 8 days of incubation, and from the limb-buds of chick embryos of 5, 6, 7, 8 or 9 days of incubation. When these suspensions were aggregated under laminar shear in a Couette viscometer or random motion in a reciprocating shaker they obeyed the theoretical relationships derived for flocculating lyophobic sols. The values of the collision efficiency found for the different cell types under given conditions were used to calculate the force of interaction between cells of each type. The force of interaction ranged between 9 × 10−11 N (8-day heart) and 3 × 10−9 N (8-day liver). The forces of interaction between cells appear to be responsible for aligning the membranes of adjacent cells with a 10–20 nm gap. It is possible to arrange the cell types in a hierarchy based on the forces of interaction between them. The possible role of these forces in cell specificity is considered.

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