scholarly journals The Alter Retina: Alternative Splicing of Retinal Genes in Health and Disease

2021 ◽  
Vol 22 (4) ◽  
pp. 1855
Author(s):  
Izarbe Aísa-Marín ◽  
Rocío García-Arroyo ◽  
Serena Mirra ◽  
Gemma Marfany
Keyword(s):  
Alternative Splicing ◽  
Genetic Diagnosis ◽  
Cell Types ◽  
Alternative Transcripts ◽  
Retinal Dystrophies ◽  
Lack Of Information ◽  
Relative Production ◽  
The Central Nervous System ◽  
Health And Disease ◽  
Time Specific

Alternative splicing of mRNA is an essential mechanism to regulate and increase the diversity of the transcriptome and proteome. Alternative splicing frequently occurs in a tissue- or time-specific manner, contributing to differential gene expression between cell types during development. Neural tissues present extremely complex splicing programs and display the highest number of alternative splicing events. As an extension of the central nervous system, the retina constitutes an excellent system to illustrate the high diversity of neural transcripts. The retina expresses retinal specific splicing factors and produces a large number of alternative transcripts, including exclusive tissue-specific exons, which require an exquisite regulation. In fact, a current challenge in the genetic diagnosis of inherited retinal diseases stems from the lack of information regarding alternative splicing of retinal genes, as a considerable percentage of mutations alter splicing or the relative production of alternative transcripts. Modulation of alternative splicing in the retina is also instrumental in the design of novel therapeutic approaches for retinal dystrophies, since it enables precision medicine for specific mutations.

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.

scholarly journals Functional immune cell–astrocyte interactions

2021 ◽  
Vol 218 (9) ◽  
Author(s):  
Liliana M. Sanmarco ◽  
Carolina M. Polonio ◽  
Michael A. Wheeler ◽  
Francisco J. Quintana
Keyword(s):  
Multiple Sclerosis ◽  
Immune Cells ◽  
Immune Cell ◽  
Neurological Diseases ◽  
Cell Types ◽  
Special Focus ◽  
Potential Value ◽  
The Central Nervous System ◽  
Health And Disease ◽  
Peripheral Immune Cells

Astrocytes are abundant glial cells in the central nervous system (CNS) that control multiple aspects of health and disease. Through their interactions with components of the blood–brain barrier (BBB), astrocytes not only regulate BBB function, they also sense molecules produced by peripheral immune cells, including cytokines. Here, we review the interactions between immune cells and astrocytes and their roles in health and neurological diseases, with a special focus on multiple sclerosis (MS). We highlight known pathways that participate in astrocyte crosstalk with microglia, NK cells, T cells, and other cell types; their contribution to the pathogenesis of neurological diseases; and their potential value as therapeutic targets.

scholarly journals Brain-Derived Extracellular Vesicles in Health and Disease: A Methodological Perspective

2021 ◽  
Vol 22 (3) ◽  
pp. 1365
Author(s):  
Santra Brenna ◽  
Christoph Krisp ◽  
Hermann Clemens Altmeppen ◽  
Tim Magnus ◽  
Berta Puig
Keyword(s):  
Extracellular Vesicles ◽  
Current Knowledge ◽  
Neurological Diseases ◽  
Genetic Material ◽  
Cell Types ◽  
Basic Knowledge ◽  
Membrane Structures ◽  
The Central Nervous System ◽  
Health And Disease ◽  
Therapeutic Tools

Extracellular vesicles (EVs) are double membrane structures released by presumably all cell types that transport and deliver lipids, proteins, and genetic material to near or distant recipient cells, thereby affecting their phenotype. The basic knowledge of their functions in healthy and diseased brain is still murky and many questions about their biology are unsolved. In neurological diseases, EVs are regarded as attractive biomarkers and as therapeutic tools due to their ability to cross the blood–brain barrier (BBB). EVs have been successfully isolated from conditioned media of primary brain cells and cerebrospinal fluid (CSF), but protocols allowing for the direct study of pathophysiological events mediated or influenced by EVs isolated from brain have only recently been published. This review aims to give a brief overview of the current knowledge of EVs’ functions in the central nervous system (CNS) and the current protocols to isolate brain-derived EVs (BDEVs) used in different publications. By comparing the proteomic analysis of some of these publications, we also assess the influence of the isolation method on the protein content of BDEVs.

scholarly journals The Impact of Estrogen and Estrogen-Like Molecules in Neurogenesis and Neurodegeneration: Beneficial or Harmful?

2021 ◽  
Vol 15 ◽  
Author(s):  
Felipe A. Bustamante-Barrientos ◽  
Maxs Méndez-Ruette ◽  
Alexander Ortloff ◽  
Patricia Luz-Crawford ◽  
Francisco J. Rivera ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Estrogen Receptors ◽  
Cell Biology ◽  
Current Knowledge ◽  
Cell Types ◽  
Proliferation And Differentiation ◽  
Neural Stem Progenitor Cells ◽  
The Central Nervous System ◽  
Health And Disease ◽  
The Impact

Estrogens and estrogen-like molecules can modify the biology of several cell types. Estrogen receptors alpha (ERα) and beta (ERβ) belong to the so-called classical family of estrogen receptors, while the G protein-coupled estrogen receptor 1 (GPER-1) represents a non-classical estrogen receptor mainly located in the plasma membrane. As estrogen receptors are ubiquitously distributed, they can modulate cell proliferation, differentiation, and survival in several tissues and organs, including the central nervous system (CNS). Estrogens can exert neuroprotective roles by acting as anti-oxidants, promoting DNA repair, inducing the expression of growth factors, and modulating cerebral blood flow. Additionally, estrogen-dependent signaling pathways are involved in regulating the balance between proliferation and differentiation of neural stem/progenitor cells (NSPCs), thus influencing neurogenic processes. Since several estrogen-based therapies are used nowadays and estrogen-like molecules, including phytoestrogens and xenoestrogens, are omnipresent in our environment, estrogen-dependent changes in cell biology and tissue homeostasis have gained attention in human health and disease. This article provides a comprehensive literature review on the current knowledge of estrogen and estrogen-like molecules and their impact on cell survival and neurodegeneration, as well as their role in NSPCs proliferation/differentiation balance and neurogenesis.

Alternative Splicing Is Responsible for the Presence of Two Tissue Factor mRNA Species in LPS Stimulated Human Monocytes

1992 ◽  
Vol 67 (02) ◽  
pp. 272-276 ◽  
Author(s):  
C Paul ◽  
E van der Logt ◽  
Pieter H Reitsma ◽  
Rogier M Bertina
Keyword(s):  
Alternative Splicing ◽  
Tissue Factor ◽  
Stop Codon ◽  
Cell Types ◽  
Northern Analysis ◽  
Human Monocytes ◽  
Mrna Species ◽  
Protein Levels ◽  
Intron 1 ◽  
Tf Gene

SummaryAlthough normally absent from the surface of all circulating cell types, tissue factor (TF) can be induced to appear on circulating monocytes by stimulants like bacterial lipopolysaccharide (LPS) and phorbolesters. Northern analysis of RNA isolated from LPS stimulated human monocytes demonstrates the presence of 2.2 kb and 3.1 kb TF mRNA species. The 2.2 kb message codes for the TF protein. As demonstrated by Northern blot analysis with a variety of TF gene probes, the 3.1 kb message arises from an alternative splicing process which fails to remove 955 bp from intron 1. Because of a stop codon in intron 1 no TF protein is produced from the 3.1 kb transcript. This larger transcript should therefore not be taken into account when comparing TF gene transcription and TF protein levels.

Neurochemistry of L-Glutamate Transport in the CNS: A Review of Thirty Years of Progress

2001 ◽  
Vol 66 (9) ◽  
pp. 1315-1340 ◽  
Author(s):  
Vladimir J. Balcar ◽  
Akiko Takamoto ◽  
Yukio Yoneda
Keyword(s):  
Molecular Biology ◽  
Glutamate Transport ◽  
Mammalian Brain ◽  
Activity Data ◽  
System A ◽  
Recent Developments ◽  
The Central Nervous System ◽  
Health And Disease ◽  
Disease Analysis

The review highlights the landmark studies leading from the discovery and initial characterization of the Na+-dependent "high affinity" uptake in the mammalian brain to the cloning of individual transporters and the subsequent expansion of the field into the realm of molecular biology. When the data and hypotheses from 1970's are confronted with the recent developments in the field, we can conclude that the suggestions made nearly thirty years ago were essentially correct: the uptake, mediated by an active transport into neurons and glial cells, serves to control the extracellular concentrations of L-glutamate and prevents the neurotoxicity. The modern techniques of molecular biology may have provided additional data on the nature and location of the transporters but the classical neurochemical approach, using structural analogues of glutamate designed as specific inhibitors or substrates for glutamate transport, has been crucial for the investigations of particular roles that glutamate transport might play in health and disease. Analysis of recent structure/activity data presented in this review has yielded a novel insight into the pharmacological characteristics of L-glutamate transport, suggesting existence of additional heterogeneity in the system, beyond that so far discovered by molecular genetics. More compounds that specifically interact with individual glutamate transporters are urgently needed for more detailed investigations of neurochemical characteristics of glutamatergic transport and its integration into the glutamatergic synapses in the central nervous system. A review with 162 references.

scholarly journals Neural Stem Cells: What Happens When They Go Viral?

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1468
Author(s):  
Yashika S. Kamte ◽  
Manisha N. Chandwani ◽  
Alexa C. Michaels ◽  
Lauren A. O’Donnell
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Viral Infections ◽  
Wide Spectrum ◽  
Cell Types ◽  
Developmental Abnormalities ◽  
Multipotent Progenitor Cells ◽  
The Central Nervous System ◽  
Simplex Virus ◽  
The Brain

Viruses that infect the central nervous system (CNS) are associated with developmental abnormalities as well as neuropsychiatric and degenerative conditions. Many of these viruses such as Zika virus (ZIKV), cytomegalovirus (CMV), and herpes simplex virus (HSV) demonstrate tropism for neural stem cells (NSCs). NSCs are the multipotent progenitor cells of the brain that have the ability to form neurons, astrocytes, and oligodendrocytes. Viral infections often alter the function of NSCs, with profound impacts on the growth and repair of the brain. There are a wide spectrum of effects on NSCs, which differ by the type of virus, the model system, the cell types studied, and the age of the host. Thus, it is a challenge to predict and define the consequences of interactions between viruses and NSCs. The purpose of this review is to dissect the mechanisms by which viruses can affect survival, proliferation, and differentiation of NSCs. This review also sheds light on the contribution of key antiviral cytokines in the impairment of NSC activity during a viral infection, revealing a complex interplay between NSCs, viruses, and the immune system.

scholarly journals Alternative splicing during mammalian organ development

2021 ◽  
Author(s):  
Pavel V. Mazin ◽  
Philipp Khaitovich ◽  
Margarida Cardoso-Moreira ◽  
Henrik Kaessmann
Keyword(s):  
Gene Expression ◽  
Alternative Splicing ◽  
Regulatory Networks ◽  
Organ Development ◽  
Functional Diversification ◽  
Mammalian Genomes ◽  
Species Comparisons ◽  
Time Specific ◽  
The Brain ◽  
Gene Expression Levels

AbstractAlternative splicing (AS) is pervasive in mammalian genomes, yet cross-species comparisons have been largely restricted to adult tissues and the functionality of most AS events remains unclear. We assessed AS patterns across pre- and postnatal development of seven organs in six mammals and a bird. Our analyses revealed that developmentally dynamic AS events, which are especially prevalent in the brain, are substantially more conserved than nondynamic ones. Cassette exons with increasing inclusion frequencies during development show the strongest signals of conserved and regulated AS. Newly emerged cassette exons are typically incorporated late in testis development, but those retained during evolution are predominantly brain specific. Our work suggests that an intricate interplay of programs controlling gene expression levels and AS is fundamental to organ development, especially for the brain and heart. In these regulatory networks, AS affords substantial functional diversification of genes through the generation of tissue- and time-specific isoforms from broadly expressed genes.

scholarly journals DNA Methylation Profiles of Tph1A and BDNF in Gut and Brain of L. Rhamnosus-Treated Zebrafish

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 142
Author(s):  
Mariella Cuomo ◽  
Luca Borrelli ◽  
Rosa Della Monica ◽  
Lorena Coretti ◽  
Giulia De Riso ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Molecular Mechanisms ◽  
The Past ◽  
Targeted Analysis ◽  
Lack Of Information ◽  
High Resolution Power ◽  
Resolution Level ◽  
Health And Disease ◽  
High Doses ◽  
The Brain

The bidirectional microbiota–gut–brain axis has raised increasing interest over the past years in the context of health and disease, but there is a lack of information on molecular mechanisms underlying this connection. We hypothesized that change in microbiota composition may affect brain epigenetics leading to long-lasting effects on specific brain gene regulation. To test this hypothesis, we used Zebrafish (Danio Rerio) as a model system. As previously shown, treatment with high doses of probiotics can modulate behavior in Zebrafish, causing significant changes in the expression of some brain-relevant genes, such as BDNF and Tph1A. Using an ultra-deep targeted analysis, we investigated the methylation state of the BDNF and Tph1A promoter region in the brain and gut of probiotic-treated and untreated Zebrafishes. Thanks to the high resolution power of our analysis, we evaluated cell-to-cell methylation differences. At this resolution level, we found slight DNA methylation changes in probiotic-treated samples, likely related to a subgroup of brain and gut cells, and that specific DNA methylation signatures significantly correlated with specific behavioral scores.

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